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Biochem J. May 1, 2002; 363(Pt 3): 417–429.
PMCID: PMC1222494

Endolysosomal proteolysis and its regulation.


The endolysosomal system comprises a unique environment for proteolysis, which is regulated in a manner that apparently does not involve protease inhibitors. The system comprises a series of membrane-bound intracellular compartments, within which endocytosed material and redundant cellular components are hydrolysed. Endocytosed material tends to flow vectorially through the system, proceeding through the early endosome, the endosome carrier vesicle, the late endosome and the lysosome. Phagocytosis and autophagy provide alternative entry points into the system. Late endosomes, lysosome/late endosome hybrid organelles, phagosomes and autophagosomes are the principal sites for proteolysis. In each case, hydrolytic competence is due to components of the endolysosomal system, i.e. proteases, lysosome-associated membrane proteins, H(+)-ATPases and possibly cysteine transporters. The view is emerging that lysosomes are organelles for the storage of hydrolases, perhaps in an inactivated form. Once a substrate has entered a proteolytically competent environment, the rate-limiting proteolytic steps are probably effected by cysteine endoproteinases. As these are affected by pH and possibly redox potential, they may be regulated by the organelle luminal environment. Regulation is probably also affected, among other factors, by organelle fusion reactions, whereby the meeting of enzyme and substrate may be controlled. Such systems would permit simultaneous regulation of a number of unrelated hydrolases.

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Selected References

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  • Gaullier JM, Gillooly D, Simonsen A, Stenmark H. Regulation of endocytic membrane traffic by phosphatidylinositol 3-phosphate. Biochem Soc Trans. 1999 Aug;27(4):666–670. [PubMed]
  • Sechi AS, Wehland J. The actin cytoskeleton and plasma membrane connection: PtdIns(4,5)P(2) influences cytoskeletal protein activity at the plasma membrane. J Cell Sci. 2000 Nov;113(Pt 21):3685–3695. [PubMed]
  • Matozaki T, Nakanishi H, Takai Y. Small G-protein networks: their crosstalk and signal cascades. Cell Signal. 2000 Aug;12(8):515–524. [PubMed]
  • Qualmann B, Kessels MM, Kelly RB. Molecular links between endocytosis and the actin cytoskeleton. J Cell Biol. 2000 Sep 4;150(5):F111–F116. [PMC free article] [PubMed]
  • Miaczynska Marta, Zerial Marino. Mosaic organization of the endocytic pathway. Exp Cell Res. 2002 Jan 1;272(1):8–14. [PubMed]
  • Clague MJ, Urbé S. The interface of receptor trafficking and signalling. J Cell Sci. 2001 Sep;114(Pt 17):3075–3081. [PubMed]
  • May RC, Machesky LM. Phagocytosis and the actin cytoskeleton. J Cell Sci. 2001 Mar;114(Pt 6):1061–1077. [PubMed]
  • Murphy RF. Maturation models for endosome and lysosome biogenesis. Trends Cell Biol. 1991 Oct;1(4):77–82. [PubMed]
  • Thilo L, Stroud E, Haylett T. Maturation of early endosomes and vesicular traffic to lysosomes in relation to membrane recycling. J Cell Sci. 1995 Apr;108(Pt 4):1791–1803. [PubMed]
  • Ghosh RN, Gelman DL, Maxfield FR. Quantification of low density lipoprotein and transferrin endocytic sorting HEp2 cells using confocal microscopy. J Cell Sci. 1994 Aug;107(Pt 8):2177–2189. [PubMed]
  • Fuchs R, Schmid S, Mellman I. A possible role for Na+,K+-ATPase in regulating ATP-dependent endosome acidification. Proc Natl Acad Sci U S A. 1989 Jan;86(2):539–543. [PMC free article] [PubMed]
  • Cain CC, Sipe DM, Murphy RF. Regulation of endocytic pH by the Na+,K+-ATPase in living cells. Proc Natl Acad Sci U S A. 1989 Jan;86(2):544–548. [PMC free article] [PubMed]
  • Mellman I. The importance of being acid: the role of acidification in intracellular membrane traffic. J Exp Biol. 1992 Nov;172:39–45. [PubMed]
  • Hopkins CR, Gibson A, Shipman M, Strickland DK, Trowbridge IS. In migrating fibroblasts, recycling receptors are concentrated in narrow tubules in the pericentriolar area, and then routed to the plasma membrane of the leading lamella. J Cell Biol. 1994 Jun;125(6):1265–1274. [PMC free article] [PubMed]
  • Gruenberg J, Griffiths G, Howell KE. Characterization of the early endosome and putative endocytic carrier vesicles in vivo and with an assay of vesicle fusion in vitro. J Cell Biol. 1989 Apr;108(4):1301–1316. [PMC free article] [PubMed]
  • Aniento F, Emans N, Griffiths G, Gruenberg J. Cytoplasmic dynein-dependent vesicular transport from early to late endosomes. J Cell Biol. 1993 Dec;123(6 Pt 1):1373–1387. [PMC free article] [PubMed]
  • Clague MJ, Urbé S, Aniento F, Gruenberg J. Vacuolar ATPase activity is required for endosomal carrier vesicle formation. J Biol Chem. 1994 Jan 7;269(1):21–24. [PubMed]
  • Killisch I, Steinlein P, Römisch K, Hollinshead R, Beug H, Griffiths G. Characterization of early and late endocytic compartments of the transferrin cycle. Transferrin receptor antibody blocks erythroid differentiation by trapping the receptor in the early endosome. J Cell Sci. 1992 Sep;103(Pt 1):211–232. [PubMed]
  • Jahraus A, Tjelle TE, Berg T, Habermann A, Storrie B, Ullrich O, Griffiths G. In vitro fusion of phagosomes with different endocytic organelles from J774 macrophages. J Biol Chem. 1998 Nov 13;273(46):30379–30390. [PubMed]
  • de Duve C. Lysosomes revisited. Eur J Biochem. 1983 Dec 15;137(3):391–397. [PubMed]
  • Butor C, Griffiths G, Aronson NN, Jr, Varki A. Co-localization of hydrolytic enzymes with widely disparate pH optima: implications for the regulation of lysosomal pH. J Cell Sci. 1995 Jun;108(Pt 6):2213–2219. [PubMed]
  • Dehrmann FM, Elliott E, Dennison C. Reductive activation markedly increases the stability of cathepsins B and L to extracellular ionic conditions. Biol Chem Hoppe Seyler. 1996 Jun;377(6):391–394. [PubMed]
  • Clague MJ. Molecular aspects of the endocytic pathway. Biochem J. 1998 Dec 1;336(Pt 2):271–282. [PMC free article] [PubMed]
  • Gruenberg J. The endocytic pathway: a mosaic of domains. Nat Rev Mol Cell Biol. 2001 Oct;2(10):721–730. [PubMed]
  • Méresse S, Gorvel JP, Chavrier P. The rab7 GTPase resides on a vesicular compartment connected to lysosomes. J Cell Sci. 1995 Nov;108(Pt 11):3349–3358. [PubMed]
  • Tjelle TE, Brech A, Juvet LK, Griffiths G, Berg T. Isolation and characterization of early endosomes, late endosomes and terminal lysosomes: their role in protein degradation. J Cell Sci. 1996 Dec;109(Pt 12):2905–2914. [PubMed]
  • Bright NA, Reaves BJ, Mullock BM, Luzio JP. Dense core lysosomes can fuse with late endosomes and are re-formed from the resultant hybrid organelles. J Cell Sci. 1997 Sep;110(Pt 17):2027–2040. [PubMed]
  • Ward DM, Leslie JD, Kaplan J. Homotypic lysosome fusion in macrophages: analysis using an in vitro assay. J Cell Biol. 1997 Nov 3;139(3):665–673. [PMC free article] [PubMed]
  • Berg T, Gjøen T, Bakke O. Physiological functions of endosomal proteolysis. Biochem J. 1995 Apr 15;307(Pt 2):313–326. [PMC free article] [PubMed]
  • Storrie B, Desjardins M. The biogenesis of lysosomes: is it a kiss and run, continuous fusion and fission process? Bioessays. 1996 Nov;18(11):895–903. [PubMed]
  • Luzio JP, Rous BA, Bright NA, Pryor PR, Mullock BM, Piper RC. Lysosome-endosome fusion and lysosome biogenesis. J Cell Sci. 2000 May;113(Pt 9):1515–1524. [PubMed]
  • Mullock BM, Bright NA, Fearon CW, Gray SR, Luzio JP. Fusion of lysosomes with late endosomes produces a hybrid organelle of intermediate density and is NSF dependent. J Cell Biol. 1998 Feb 9;140(3):591–601. [PMC free article] [PubMed]
  • Pryor PR, Mullock BM, Bright NA, Gray SR, Luzio JP. The role of intraorganellar Ca(2+) in late endosome-lysosome heterotypic fusion and in the reformation of lysosomes from hybrid organelles. J Cell Biol. 2000 May 29;149(5):1053–1062. [PMC free article] [PubMed]
  • Andrews NW. Regulated secretion of conventional lysosomes. Trends Cell Biol. 2000 Aug;10(8):316–321. [PubMed]
  • Martinez I, Chakrabarti S, Hellevik T, Morehead J, Fowler K, Andrews NW. Synaptotagmin VII regulates Ca(2+)-dependent exocytosis of lysosomes in fibroblasts. J Cell Biol. 2000 Mar 20;148(6):1141–1149. [PMC free article] [PubMed]
  • Reddy A, Caler EV, Andrews NW. Plasma membrane repair is mediated by Ca(2+)-regulated exocytosis of lysosomes. Cell. 2001 Jul 27;106(2):157–169. [PubMed]
  • Denzer K, Kleijmeer MJ, Heijnen HF, Stoorvogel W, Geuze HJ. Exosome: from internal vesicle of the multivesicular body to intercellular signaling device. J Cell Sci. 2000 Oct;113(Pt 19):3365–3374. [PubMed]
  • Warnock DG. Regulation of endosomal acidification via Gi-type protein. Kidney Int. 1999 Jun;55(6):2524–2525. [PubMed]
  • Rabinowitz S, Horstmann H, Gordon S, Griffiths G. Immunocytochemical characterization of the endocytic and phagolysosomal compartments in peritoneal macrophages. J Cell Biol. 1992 Jan;116(1):95–112. [PMC free article] [PubMed]
  • Seglen PO, Bohley P. Autophagy and other vacuolar protein degradation mechanisms. Experientia. 1992 Feb 15;48(2):158–172. [PubMed]
  • Blommaart EF, Luiken JJ, Meijer AJ. Autophagic proteolysis: control and specificity. Histochem J. 1997 May;29(5):365–385. [PubMed]
  • Mortimore GE, Lardeux BR, Adams CE. Regulation of microautophagy and basal protein turnover in rat liver. Effects of short-term starvation. J Biol Chem. 1988 Feb 15;263(5):2506–2512. [PubMed]
  • Mortimore GE, Hutson NJ, Surmacz CA. Quantitative correlation between proteolysis and macro- and microautophagy in mouse hepatocytes during starvation and refeeding. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2179–2183. [PMC free article] [PubMed]
  • Cuervo AM, Dice JF. Lysosomes, a meeting point of proteins, chaperones, and proteases. J Mol Med (Berl) 1998 Jan;76(1):6–12. [PubMed]
  • Kim J, Klionsky DJ. Autophagy, cytoplasm-to-vacuole targeting pathway, and pexophagy in yeast and mammalian cells. Annu Rev Biochem. 2000;69:303–342. [PubMed]
  • Pfeifer U. Inhibition by insulin of the formation of autophagic vacuoles in rat liver. A morphometric approach to the kinetics of intracellular degradation by autophagy. J Cell Biol. 1978 Jul;78(1):152–167. [PMC free article] [PubMed]
  • Dunn WA., Jr Studies on the mechanisms of autophagy: formation of the autophagic vacuole. J Cell Biol. 1990 Jun;110(6):1923–1933. [PMC free article] [PubMed]
  • Dunn WA., Jr Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. J Cell Biol. 1990 Jun;110(6):1935–1945. [PMC free article] [PubMed]
  • Ogier-Denis E, Couvineau A, Maoret JJ, Houri JJ, Bauvy C, De Stefanis D, Isidoro C, Laburthe M, Codogno P. A heterotrimeric Gi3-protein controls autophagic sequestration in the human colon cancer cell line HT-29. J Biol Chem. 1995 Jan 6;270(1):13–16. [PubMed]
  • Ogier-Denis E, Houri JJ, Bauvy C, Codogno P. Guanine nucleotide exchange on heterotrimeric Gi3 protein controls autophagic sequestration in HT-29 cells. J Biol Chem. 1996 Nov 8;271(45):28593–28600. [PubMed]
  • Petiot A, Ogier-Denis E, Bauvy C, Cluzeaud F, Vandewalle A, Codogno P. Subcellular localization of the Galphai3 protein and G alpha interacting protein, two proteins involved in the control of macroautophagy in human colon cancer HT-29 cells. Biochem J. 1999 Jan 15;337(Pt 2):289–295. [PMC free article] [PubMed]
  • Mizushima N, Sugita H, Yoshimori T, Ohsumi Y. A new protein conjugation system in human. The counterpart of the yeast Apg12p conjugation system essential for autophagy. J Biol Chem. 1998 Dec 18;273(51):33889–33892. [PubMed]
  • Kirisako T, Baba M, Ishihara N, Miyazawa K, Ohsumi M, Yoshimori T, Noda T, Ohsumi Y. Formation process of autophagosome is traced with Apg8/Aut7p in yeast. J Cell Biol. 1999 Oct 18;147(2):435–446. [PMC free article] [PubMed]
  • Yamamoto A, Masaki R, Fukui Y, Tashiro Y. Absence of cytochrome P-450 and presence of autolysosomal membrane antigens on the isolation membranes and autophagosomal membranes in rat hepatocytes. J Histochem Cytochem. 1990 Nov;38(11):1571–1581. [PubMed]
  • Yamamoto A, Masaki R, Tashiro Y. Characterization of the isolation membranes and the limiting membranes of autophagosomes in rat hepatocytes by lectin cytochemistry. J Histochem Cytochem. 1990 Apr;38(4):573–580. [PubMed]
  • Lawrence BP, Brown WJ. Autophagic vacuoles rapidly fuse with pre-existing lysosomes in cultured hepatocytes. J Cell Sci. 1992 Jul;102(Pt 3):515–526. [PubMed]
  • Gordon PB, Seglen PO. Prelysosomal convergence of autophagic and endocytic pathways. Biochem Biophys Res Commun. 1988 Feb 29;151(1):40–47. [PubMed]
  • Tooze J, Hollinshead M, Ludwig T, Howell K, Hoflack B, Kern H. In exocrine pancreas, the basolateral endocytic pathway converges with the autophagic pathway immediately after the early endosome. J Cell Biol. 1990 Aug;111(2):329–345. [PMC free article] [PubMed]
  • Rabouille C, Strous GJ, Crapo JD, Geuze HJ, Slot JW. The differential degradation of two cytosolic proteins as a tool to monitor autophagy in hepatocytes by immunocytochemistry. J Cell Biol. 1993 Feb;120(4):897–908. [PMC free article] [PubMed]
  • Strømhaug PE, Seglen PO. Evidence for acidity of prelysosomal autophagic/endocytic vacuoles (amphisomes). Biochem J. 1993 Apr 1;291(Pt 1):115–121. [PMC free article] [PubMed]
  • van Oss CJ. Phagocytosis: an overview. Methods Enzymol. 1986;132:3–15. [PubMed]
  • Kwiatkowska K, Sobota A. Signaling pathways in phagocytosis. Bioessays. 1999 May;21(5):422–431. [PubMed]
  • Mayorga LS, Bertini F, Stahl PD. Fusion of newly formed phagosomes with endosomes in intact cells and in a cell-free system. J Biol Chem. 1991 Apr 5;266(10):6511–6517. [PubMed]
  • Pitt A, Mayorga LS, Schwartz AL, Stahl PD. Transport of phagosomal components to an endosomal compartment. J Biol Chem. 1992 Jan 5;267(1):126–132. [PubMed]
  • Desjardins M, Huber LA, Parton RG, Griffiths G. Biogenesis of phagolysosomes proceeds through a sequential series of interactions with the endocytic apparatus. J Cell Biol. 1994 Mar;124(5):677–688. [PMC free article] [PubMed]
  • Mellman I, Fuchs R, Helenius A. Acidification of the endocytic and exocytic pathways. Annu Rev Biochem. 1986;55:663–700. [PubMed]
  • Claus V, Jahraus A, Tjelle T, Berg T, Kirschke H, Faulstich H, Griffiths G. Lysosomal enzyme trafficking between phagosomes, endosomes, and lysosomes in J774 macrophages. Enrichment of cathepsin H in early endosomes. J Biol Chem. 1998 Apr 17;273(16):9842–9851. [PubMed]
  • Sturgill-Koszycki S, Schlesinger PH, Chakraborty P, Haddix PL, Collins HL, Fok AK, Allen RD, Gluck SL, Heuser J, Russell DG. Lack of acidification in Mycobacterium phagosomes produced by exclusion of the vesicular proton-ATPase. Science. 1994 Feb 4;263(5147):678–681. [PubMed]
  • Via LE, Deretic D, Ulmer RJ, Hibler NS, Huber LA, Deretic V. Arrest of mycobacterial phagosome maturation is caused by a block in vesicle fusion between stages controlled by rab5 and rab7. J Biol Chem. 1997 May 16;272(20):13326–13331. [PubMed]
  • Hasilik A. The early and late processing of lysosomal enzymes: proteolysis and compartmentation. Experientia. 1992 Feb 15;48(2):130–151. [PubMed]
  • Kornfeld S. Trafficking of lysosomal enzymes in normal and disease states. J Clin Invest. 1986 Jan;77(1):1–6. [PMC free article] [PubMed]
  • Bohley P, Seglen PO. Proteases and proteolysis in the lysosome. Experientia. 1992 Feb 15;48(2):151–157. [PubMed]
  • Tikkanen R, Peltola M, Oinonen C, Rouvinen J, Peltonen L. Several cooperating binding sites mediate the interaction of a lysosomal enzyme with phosphotransferase. EMBO J. 1997 Nov 17;16(22):6684–6693. [PMC free article] [PubMed]
  • Cuozzo JW, Tao K, Cygler M, Mort JS, Sahagian GG. Lysine-based structure responsible for selective mannose phosphorylation of cathepsin D and cathepsin L defines a common structural motif for lysosomal enzyme targeting. J Biol Chem. 1998 Aug 14;273(33):21067–21076. [PubMed]
  • Lukong KE, Elsliger MA, Mort JS, Potier M, Pshezhetsky AV. Identification of UDP-N-acetylglucosamine-phosphotransferase-binding sites on the lysosomal proteases, cathepsins A, B, and D. Biochemistry. 1999 Jan 5;38(1):73–80. [PubMed]
  • Ludwig T, Le Borgne R, Hoflack B. Roles for mannose-6-phosphate receptors in lysosomal enzyme sorting, IGF-II binding and clathrin-coat assembly. Trends Cell Biol. 1995 May;5(5):202–206. [PubMed]
  • Storer AC, Ménard R. Catalytic mechanism in papain family of cysteine peptidases. Methods Enzymol. 1994;244:486–500. [PubMed]
  • Peters C, von Figura K. Biogenesis of lysosomal membranes. FEBS Lett. 1994 Jun 6;346(1):108–114. [PubMed]
  • Guarnieri FG, Arterburn LM, Penno MB, Cha Y, August JT. The motif Tyr-X-X-hydrophobic residue mediates lysosomal membrane targeting of lysosome-associated membrane protein 1. J Biol Chem. 1993 Jan 25;268(3):1941–1946. [PubMed]
  • Karlsson K, Carlsson SR. Sorting of lysosomal membrane glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network. J Biol Chem. 1998 Jul 24;273(30):18966–18973. [PubMed]
  • Jadot M, Dubois F, Wattiaux-De Coninck S, Wattiaux R. Supramolecular assemblies from lysosomal matrix proteins and complex lipids. Eur J Biochem. 1997 Nov 1;249(3):862–869. [PubMed]
  • Silverstein RL, Febbraio M. Identification of lysosome-associated membrane protein-2 as an activation-dependent platelet surface glycoprotein. Blood. 1992 Sep 15;80(6):1470–1475. [PubMed]
  • Andrejewski N, Punnonen EL, Guhde G, Tanaka Y, Lüllmann-Rauch R, Hartmann D, von Figura K, Saftig P. Normal lysosomal morphology and function in LAMP-1-deficient mice. J Biol Chem. 1999 Apr 30;274(18):12692–12701. [PubMed]
  • Tanaka Y, Guhde G, Suter A, Eskelinen EL, Hartmann D, Lüllmann-Rauch R, Janssen PM, Blanz J, von Figura K, Saftig P. Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature. 2000 Aug 24;406(6798):902–906. [PubMed]
  • Pisoni RL, Thoene JG. The transport systems of mammalian lysosomes. Biochim Biophys Acta. 1991 Dec 12;1071(4):351–373. [PubMed]
  • Lloyd JB. Lysosomal handling of cystine residues: stoichiometry of cysteine involvement. Biochem J. 1992 Sep 15;286(Pt 3):979–980. [PMC free article] [PubMed]
  • Pisoni RL, Acker TL, Lisowski KM, Lemons RM, Thoene JG. A cysteine-specific lysosomal transport system provides a major route for the delivery of thiol to human fibroblast lysosomes: possible role in supporting lysosomal proteolysis. J Cell Biol. 1990 Feb;110(2):327–335. [PMC free article] [PubMed]
  • Pisoni RL, Velilla VQ. Evidence for an essential histidine residue located in the binding site of the cysteine-specific lysosomal transport protein. Biochim Biophys Acta. 1995 May 24;1236(1):23–30. [PubMed]
  • Gainey D, Short S, McCoy KL. Intracellular location of cysteine transport activity correlates with productive processing of antigen disulfide. J Cell Physiol. 1996 Aug;168(2):248–254. [PubMed]
  • Feener EP, Shen WC, Ryser HJ. Cleavage of disulfide bonds in endocytosed macromolecules. A processing not associated with lysosomes or endosomes. J Biol Chem. 1990 Nov 5;265(31):18780–18785. [PubMed]
  • Collins DS, Unanue ER, Harding CV. Reduction of disulfide bonds within lysosomes is a key step in antigen processing. J Immunol. 1991 Dec 15;147(12):4054–4059. [PubMed]
  • Collier RJ, Kandel J. Structure and activity of diphtheria toxin. I. Thiol-dependent dissociation of a fraction of toxin into enzymically active and inactive fragments. J Biol Chem. 1971 Mar 10;246(5):1496–1503. [PubMed]
  • Moskaug JO, Sandvig K, Olsnes S. Cell-mediated reduction of the interfragment disulfide in nicked diphtheria toxin. A new system to study toxin entry at low pH. J Biol Chem. 1987 Jul 25;262(21):10339–10345. [PubMed]
  • Merkel BJ, Mandel R, Ryser HJ, McCoy KL. Characterization of fibroblasts with a unique defect in processing antigens with disulfide bonds. J Immunol. 1995 Jan 1;154(1):128–136. [PubMed]
  • Hampl J, Gradehandt G, Kalbacher H, Rüde E. In vitro processing of insulin for recognition by murine T cells results in the generation of A chains with free CysSH. J Immunol. 1992 May 1;148(9):2664–2671. [PubMed]
  • Wilcox D, Mason RW. Inhibition of cysteine proteinases in lysosomes and whole cells. Biochem J. 1992 Jul 15;285(Pt 2):495–502. [PMC free article] [PubMed]
  • Krepela E, Procházka J, Kárová B, Cermák J, Roubková H. Cathepsin B, thiols and cysteine protease inhibitors in squamous-cell lung cancer. Neoplasma. 1997;44(4):219–239. [PubMed]
  • Krepela E, Procházka J, Kárová B. Regulation of cathepsin B activity by cysteine and related thiols. Biol Chem. 1999 May;380(5):541–551. [PubMed]
  • Kooistra T, Millard PC, Lloyd JB. Role of thiols in degradation of proteins by cathepsins. Biochem J. 1982 May 15;204(2):471–477. [PMC free article] [PubMed]
  • Mego JL. Role of thiols, pH and cathepsin D in the lysosomal catabolism of serum albumin. Biochem J. 1984 Mar 15;218(3):775–783. [PMC free article] [PubMed]
  • Hwang C, Sinskey AJ, Lodish HF. Oxidized redox state of glutathione in the endoplasmic reticulum. Science. 1992 Sep 11;257(5076):1496–1502. [PubMed]
  • Frand AR, Cuozzo JW, Kaiser CA. Pathways for protein disulphide bond formation. Trends Cell Biol. 2000 May;10(5):203–210. [PubMed]
  • Arunachalam B, Phan UT, Geuze HJ, Cresswell P. Enzymatic reduction of disulfide bonds in lysosomes: characterization of a gamma-interferon-inducible lysosomal thiol reductase (GILT). Proc Natl Acad Sci U S A. 2000 Jan 18;97(2):745–750. [PMC free article] [PubMed]
  • Gahl WA, Tietze F. pH effects on cystine transport in lysosome-rich leucocyte granular fractions. Biochem J. 1985 May 15;228(1):263–267. [PMC free article] [PubMed]
  • Gille L, Nohl H. The existence of a lysosomal redox chain and the role of ubiquinone. Arch Biochem Biophys. 2000 Mar 15;375(2):347–354. [PubMed]
  • Futai M, Oka T, Moriyama Y, Wada Y. Diverse roles of single membrane organelles: factors establishing the acid lumenal pH. J Biochem. 1998 Aug;124(2):259–267. [PubMed]
  • Feng Y, Forgac M. Inhibition of vacuolar H(+)-ATPase by disulfide bond formation between cysteine 254 and cysteine 532 in subunit A. J Biol Chem. 1994 May 6;269(18):13224–13230. [PubMed]
  • Forgac M. Structure, function and regulation of the vacuolar (H+)-ATPases. FEBS Lett. 1998 Dec 4;440(3):258–263. [PubMed]
  • Forgac M. Structure and properties of the vacuolar (H+)-ATPases. J Biol Chem. 1999 May 7;274(19):12951–12954. [PubMed]
  • Reijngoud DJ, Tager JM. The permeability properties of the lysosomal membrane. Biochim Biophys Acta. 1977 Nov 14;472(3-4):419–449. [PubMed]
  • Moriyama Y, Maeda M, Futai M. Involvement of a non-proton pump factor (possibly Donnan-type equilibrium) in maintenance of an acidic pH in lysosomes. FEBS Lett. 1992 May 4;302(1):18–20. [PubMed]
  • Willenbrock F, Brocklehurst K. A general framework of cysteine-proteinase mechanism deduced from studies on enzymes with structurally different analogous catalytic-site residues Asp-158 and -161 (papain and actinidin), Gly-196 (cathepsin B) and Asn-165 (cathepsin H). Kinetic studies up to pH 8 of the hydrolysis of N-alpha-benzyloxycarbonyl-L-arginyl-L-arginine 2-naphthylamide catalysed by cathepsin B and of L-arginine 2-naphthylamide catalysed by cathepsin H. Biochem J. 1985 Apr 15;227(2):521–528. [PMC free article] [PubMed]
  • Khouri HE, Plouffe C, Hasnain S, Hirama T, Storer AC, Ménard R. A model to explain the pH-dependent specificity of cathepsin B-catalysed hydrolyses. Biochem J. 1991 May 1;275(Pt 3):751–757. [PMC free article] [PubMed]
  • Hasnain S, Hirama T, Tam A, Mort JS. Characterization of recombinant rat cathepsin B and nonglycosylated mutants expressed in yeast. New insights into the pH dependence of cathepsin B-catalyzed hydrolyses. J Biol Chem. 1992 Mar 5;267(7):4713–4721. [PubMed]
  • Moin K, Day NA, Sameni M, Hasnain S, Hirama T, Sloane BF. Human tumour cathepsin B. Comparison with normal liver cathepsin B. Biochem J. 1992 Jul 15;285(Pt 2):427–434. [PMC free article] [PubMed]
  • Bakker AC, Webster P, Jacob WA, Andrews NW. Homotypic fusion between aggregated lysosomes triggered by elevated [Ca2+]i in fibroblasts. J Cell Sci. 1997 Sep;110(Pt 18):2227–2238. [PubMed]
  • Jaconi ME, Lew DP, Carpentier JL, Magnusson KE, Sjögren M, Stendahl O. Cytosolic free calcium elevation mediates the phagosome-lysosome fusion during phagocytosis in human neutrophils. J Cell Biol. 1990 May;110(5):1555–1564. [PMC free article] [PubMed]
  • Malik ZA, Iyer SS, Kusner DJ. Mycobacterium tuberculosis phagosomes exhibit altered calmodulin-dependent signal transduction: contribution to inhibition of phagosome-lysosome fusion and intracellular survival in human macrophages. J Immunol. 2001 Mar 1;166(5):3392–3401. [PubMed]
  • Gordon PB, Holen I, Fosse M, Røtnes JS, Seglen PO. Dependence of hepatocytic autophagy on intracellularly sequestered calcium. J Biol Chem. 1993 Dec 15;268(35):26107–26112. [PubMed]
  • Haller T, Völkl H, Deetjen P, Dietl P. The lysosomal Ca2+ pool in MDCK cells can be released by ins(1,4,5)P3-dependent hormones or thapsigargin but does not activate store-operated Ca2+ entry. Biochem J. 1996 Nov 1;319(Pt 3):909–912. [PMC free article] [PubMed]
  • Lemons RM, Thoene JG. Mediated calcium transport by isolated human fibroblast lysosomes. J Biol Chem. 1991 Aug 5;266(22):14378–14382. [PubMed]
  • Carafoli E. Intracellular calcium homeostasis. Annu Rev Biochem. 1987;56:395–433. [PubMed]
  • Kostoulas G, Hörler D, Naggi A, Casu B, Baici A. Electrostatic interactions between human leukocyte elastase and sulfated glycosaminoglycans: physiological implications. Biol Chem. 1997 Dec;378(12):1481–1489. [PubMed]
  • Colomer V, Kicska GA, Rindler MJ. Secretory granule content proteins and the luminal domains of granule membrane proteins aggregate in vitro at mildly acidic pH. J Biol Chem. 1996 Jan 5;271(1):48–55. [PubMed]
  • Buckmaster MJ, Ferris AL, Storrie B. Effects of pH, detergent and salt on aggregation of Chinese-hamster-ovary-cell lysosomal enzymes. Biochem J. 1988 Feb 1;249(3):921–923. [PMC free article] [PubMed]
  • Henning R, Plattner H, Stoffel W. Nature and localization of acidic groups on lysosomal membranes. Biochim Biophys Acta. 1973 Nov 30;330(1):61–75. [PubMed]
  • Dehrmann FM, Coetzer TH, Pike RN, Dennison C. Mature cathepsin L is substantially active in the ionic milieu of the extracellular medium. Arch Biochem Biophys. 1995 Dec 1;324(1):93–98. [PubMed]
  • Kominami E, Hashida S, Khairallah EA, Katunuma N. Sequestration of cytoplasmic enzymes in an autophagic vacuole-lysosomal system induced by injection of leupeptin. J Biol Chem. 1983 May 25;258(10):6093–6100. [PubMed]
  • Cavalli V, Vilbois F, Corti M, Marcote MJ, Tamura K, Karin M, Arkinstall S, Gruenberg J. The stress-induced MAP kinase p38 regulates endocytic trafficking via the GDI:Rab5 complex. Mol Cell. 2001 Feb;7(2):421–432. [PubMed]
  • Miura K, Miyazawa S, Furuta S, Mitsushita J, Kamijo K, Ishida H, Miki T, Suzukawa K, Resau J, Copeland TD, et al. The Sos1-Rac1 signaling. Possible involvement of a vacuolar H(+)-ATPase E subunit. J Biol Chem. 2001 Dec 7;276(49):46276–46283. [PubMed]
  • Lamaze C, Chuang TH, Terlecky LJ, Bokoch GM, Schmid SL. Regulation of receptor-mediated endocytosis by Rho and Rac. Nature. 1996 Jul 11;382(6587):177–179. [PubMed]

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