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

被引：429

作者：

Benador, Ilan Y. ^{[1
,2
,3
]}

Veliova, Michaela ^{[1
,2
]}

Mahdaviani, Kiana ^{[3
]}

Petcherski, Anton ^{[1
,2
]}

Wikstrom, Jakob D. ^{[4
]}

Assali, Essam A. ^{[1
,2
,5
]}

Acin-Perez, Rebeca ^{[1
,2
]}

Shum, Michael ^{[1
,2
]}

Oliveira, Marcus F. ^{[6
]}

Cinti, Saverio ^{[7
]}

Sztalryd, Carole ^{[8
]}

Barshop, William D. ^{[9
]}

Wohlschlegel, James A. ^{[9
]}

Corkey, Barbara E. ^{[3
]}

Liesa, Marc ^{[1
,2
]}

Shirihai, Orian S. ^{[1
,2
,3
,5
]}

机构：

[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Endocrinol, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA

[3] Boston Univ, Sch Med, Dept Med, Obes Res Ctr, Boston, MA 02118 USA

[4] Karolinska Inst, Dept Med, Dermatol & Venereol Unit, Stockholm, Sweden

[5] Ben Gurion Univ Negev, Sch Med, Dept Clin Biochem, Beer Sheva, Israel

[6] Univ Fed Rio de Janeiro, Inst Med Biochem Leopoldo de Meis, Rio De Janeiro, Brazil

[7] Univ Ancona, Dept Expt & Clin Med, Ancona, Italy

[8] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA

[9] Univ Calif Los Angeles, David Geffen Sch Med, Dept Biol Chem, Los Angeles, CA 90095 USA

来源：

CELL METABOLISM | 2018年 / 27卷 / 04期

关键词：

BROWN ADIPOSE-TISSUE; PERILIPIN; 5; FUSION; PROTEIN; MFN2; TRANSLOCATION; TRAFFICKING; EXPRESSION; FISSION; OBESITY;

D O I：

10.1016/j.cmet.2018.03.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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 beta-oxidation capacity and depart from LDs upon activation of brown adipose tissue thermogenesis and beta-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.

引用

页码：869 / +

页数：23

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