Format

Send to

Choose Destination
Biophys J. 2014 Aug 19;107(4):879-90. doi: 10.1016/j.bpj.2014.07.015.

Interplay of packing and flip-flop in local bilayer deformation. How phosphatidylglycerol could rescue mitochondrial function in a cardiolipin-deficient yeast mutant.

Author information

1
UPMC Université Paris 06, UMR 168, Institut Curie, Paris, France; CNRS, UMR 168, Institut Curie, Paris, France.
2
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey.
3
Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, New Jersey; Department of Physics, Princeton University, Princeton, New Jersey.
4
Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France. Electronic address: michel.seigneuret@univ-paris-diderot.fr.
5
Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France.
6
Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France; Department of Physics-UFR 925, Université Pierre et Marie Curie, Paris, France.
7
Departament de Matemàtica Aplicada III, LaCàN, Universitat Politècnica de Catalunya, Barcelona, Spain.
8
Université Paris Diderot-Paris 7, Matière et Systèmes Complexes CNRS UMR 7057, Paris, France; Department of Physics-UFR 925, Université Pierre et Marie Curie, Paris, France. Electronic address: miglena.anguelova@upmc.fr.

Abstract

In a previous work, we have shown that a spatially localized transmembrane pH gradient, produced by acid micro-injection near the external side of cardiolipin-containing giant unilamellar vesicles, leads to the formation of tubules that retract after the dissipation of this gradient. These tubules have morphologies similar to mitochondrial cristae. The tubulation effect is attributable to direct phospholipid packing modification in the outer leaflet, that is promoted by protonation of cardiolipin headgroups. In this study, we compare the case of cardiolipin-containing giant unilamellar vesicles with that of giant unilamellar vesicles that contain phosphatidylglycerol (PG). Local acidification also promotes formation of tubules in the latter. However, compared with cardiolipin-containing giant unilamellar vesicles the tubules are longer, exhibit a visible pearling, and have a much longer lifetime after acid micro-injection is stopped. We attribute these differences to an additional mechanism that increases monolayer surface imbalance, namely inward PG flip-flop promoted by the local transmembrane pH gradient. Simulations using a fully nonlinear membrane model as well as geometrical calculations are in agreement with this hypothesis. Interestingly, among yeast mutants deficient in cardiolipin biosynthesis, only the crd1-null mutant, which accumulates phosphatidylglycerol, displays significant mitochondrial activity. Our work provides a possible explanation of such a property and further emphasizes the salient role of specific lipids in mitochondrial function.

PMID:
25140423
PMCID:
PMC4142233
DOI:
10.1016/j.bpj.2014.07.015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center