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Cell Metab. 2018 Apr 3;27(4):869-885.e6. doi: 10.1016/j.cmet.2018.03.003.

Mitochondria Bound to Lipid Droplets Have Unique Bioenergetics, Composition, and Dynamics that Support Lipid Droplet Expansion.

Author information

1
Division of Endocrinology, Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
2
Division of Endocrinology, Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
3
Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
4
Dermatology and Venereology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Dermato-Venereology, Karolinska University Hospital, Stockholm, Sweden.
5
Division of Endocrinology, Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Department of Clinical Biochemistry, School of Medicine, Ben Gurion University of The Negev, Beer-Sheva, Israel.
6
Institute of Medical Biochemistry Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
7
Department of Experimental and Clinical Medicine, University of Ancona, Ancona, Italy.
8
Department of Medicine, School of Medicine, University of Maryland Baltimore, MD, USA.
9
Department of Biological Chemistry, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
10
Division of Endocrinology, Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA. Electronic address: mliesa@mednet.ucla.edu.
11
Division of Endocrinology, Department of Medicine, and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Obesity Research Center, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Department of Clinical Biochemistry, School of Medicine, Ben Gurion University of The Negev, Beer-Sheva, Israel. Electronic address: oshirihai@mednet.ucla.edu.

Abstract

Mitochondria associate with lipid droplets (LDs) in fat-oxidizing tissues, but the functional role of these peridroplet mitochondria (PDM) is unknown. Microscopic observation of interscapular brown adipose tissue reveals that PDM have unique protein composition and cristae structure and remain adherent to the LD in the tissue homogenate. We developed an approach to isolate PDM based on their adherence to LDs. Comparison of purified PDM to cytoplasmic mitochondria reveals that (1) PDM have increased pyruvate oxidation, electron transport, and ATP synthesis capacities; (2) PDM have reduced β-oxidation capacity and depart from LDs upon activation of brown adipose tissue thermogenesis and β-oxidation; (3) PDM support LD expansion as Perilipin5-induced recruitment of mitochondria to LDs increases ATP synthase-dependent triacylglyceride synthesis; and (4) PDM maintain a distinct protein composition due to uniquely low fusion-fission dynamics. We conclude that PDM represent a segregated mitochondrial population with unique structure and function that supports triacylglyceride synthesis.

KEYWORDS:

brown adipose tissue; lipid droplet; mitochondria; mitochondrial dynamics; peridroplet mitochondria

PMID:
29617645
PMCID:
PMC5969538
DOI:
10.1016/j.cmet.2018.03.003
[Indexed for MEDLINE]
Free PMC Article

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