Sirtuin 5 protects mitochondria from fragmentation and degradation during starvation.
During starvation, intra-mitochondrial sirtuins, NAD+sensitive deacylating enzymes that modulate metabolic homeostasis and survival, directly adjust mitochondrial function to nutrient availability; concomitantly, mitochondria elongate to escape autophagic degradation. However, whether sirtuins also impinge on mitochondrial dynamics is still uncharacterized. Here we show that the mitochondrial Sirtuin 5 (Sirt5) is essential for starvation induced mitochondrial elongation. Deletion of Sirt5 in mouse embryonic fibroblasts increased levels of mitochondrial dynamics of 51kDa protein and mitochondrial fission protein 1, leading to mitochondrial accumulation of the pro-fission dynamin related protein 1 and to mitochondrial fragmentation. During starvation, Sirt5 deletion blunted mitochondrial elongation, resulting in increased mitophagy. Our results indicate that starvation induced mitochondrial elongation and evasion from autophagic degradation requires the energy sensor Sirt5.
Department of Biology, University of Moncton, NB, Canada.
Hala
H
Guedouari
Department of Biology, University of Moncton, NB, Canada.
Tanya
T
Daigle
Dulbecco Telethon Institute, Venetian Institute of Molecular Medicine, Padua, Italy; Department of Biology, University of Padua, Italy.
Luca
L
Scorrano
Department of Biology, University of Moncton, NB, Canada. Electronic address: etienne.hebert.chatelain@umoncton.ca.
Etienne
E
Hebert-Chatelain
D000818:Animals; D001343:Autophagy / Q000187:drug effects; D002461:Cell Line, Transformed; D003470:Culture Media / Q000494:pharmacology; D034281:Dynamins / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017353:Gene Deletion; D005947:Glucose / Q000172:deficiency / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000187:drug effects* / Q000235:genetics; D063306:Mitophagy / Q000187:drug effects; D065840:Protective Factors; D037761:Sirtuins / Q000172:deficiency / Q000235:genetics*; D013312:Stress, Physiological
D003470:Culture Media; C542554:SIRT5 protein, mouse; D037761:Sirtuins; C486391:Dnm1l protein, mouse; D034281:Dynamins; D005947:Glucose
Mitochondrial degradation; Mitochondrial fragmentation; Sirtuin 5