Rheb Regulates Mitophagy Induced by Mitochondrial Energetic Status

被引：223

作者：

Melser, Su ^{[1
,6
]}

Chatelain, Etienne Hebert ^{[2
,6
]}

Lavie, Julie ^{[1
,6
]}

Mahfouf, Walid ^{[5
,6
]}

Jose, Caroline ^{[1
,6
]}

Obre, Emilie ^{[1
,6
]}

Goorden, Susan ^{[3
]}

Priault, Muriel ^{[4
,6
]}

Elgersma, Ype ^{[3
]}

Rezvani, Hamid Reza ^{[5
,6
]}

Rossignol, Rodrigue ^{[1
,6
]}

Benard, Giovanni ^{[2
,6
]}

机构：

[1] EA4576, F-33000 Bordeaux, France

[2] INSERM, U862, F-33076 Bordeaux, France

[3] Erasmus Univ, Med Ctr, Dept Neurosci, NL-3015 GD Rotterdam, Netherlands

[4] CNRS, IBGC, UMR 5095, F-33076 Bordeaux, France

[5] INSERM, U1035, F-33076 Bordeaux, France

[6] Univ Bordeaux 2, F-33076 Bordeaux, France

来源：

CELL METABOLISM | 2013年 / 17卷 / 05期

关键词：

MAMMALIAN TARGET; AUTOPHAGY; CELLS; BIOGENESIS; ACTIVATION; PATHWAY; GTPASE; PARKIN; FKBP38; LOCALIZATION;

D O I：

10.1016/j.cmet.2013.03.014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mitophagy has been recently described as a mechanism of elimination of damaged organelles. Although the regulation of the amount of mitochondria is a core issue concerning cellular energy homeostasis, the relationship between mitochondrial degradation and energetic activity has not yet been considered. Here, we report that the stimulation of mitochondrial oxidative phosphorylation enhances mitochondrial renewal by increasing its degradation rate. Upon high oxidative phosphorylation activity, we found that the small GTPase Rheb is recruited to the mitochondrial outer membrane. This mitochondrial localization of Rheb promotes mitophagy through a physical interaction with the mitochondrial autophagic receptor Nix and the autophagosomal protein LC3-II. Thus, Rheb-dependent mitophagy contributes to the maintenance of optimal mitochondrial energy production. Our data suggest that mitochondrial degradation contributes to a bulk renewal of the organelle in order to prevent mitochondrial aging and to maintain the efficiency of oxidative phosphorylation.

引用

页码：719 / 730

页数：12

共 43 条

[1] Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 [J].