Format

Send to

Choose Destination
Nature. 2015 May 28;521(7553):525-8. doi: 10.1038/nature14300. Epub 2015 Apr 20.

Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans.

Author information

1
1] Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Nikolaou Plastira 100, Heraklion 70013, Crete, Greece [2] Department of Biology, University of Crete, Heraklion 70013, Crete, Greece.
2
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Nikolaou Plastira 100, Heraklion 70013, Crete, Greece.
3
1] Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas, Nikolaou Plastira 100, Heraklion 70013, Crete, Greece [2] Department of Basic Sciences, Faculty of Medicine, University of Crete, Heraklion 71110, Crete, Greece.

Abstract

Impaired mitochondrial maintenance in disparate cell types is a shared hallmark of many human pathologies and ageing. How mitochondrial biogenesis coordinates with the removal of damaged or superfluous mitochondria to maintain cellular homeostasis is not well understood. Here we show that mitophagy, a selective type of autophagy targeting mitochondria for degradation, interfaces with mitochondrial biogenesis to regulate mitochondrial content and longevity in Caenorhabditis elegans. We find that DCT-1 is a key mediator of mitophagy and longevity assurance under conditions of stress in C. elegans. Impairment of mitophagy compromises stress resistance and triggers mitochondrial retrograde signalling through the SKN-1 transcription factor that regulates both mitochondrial biogenesis genes and mitophagy by enhancing DCT-1 expression. Our findings reveal a homeostatic feedback loop that integrates metabolic signals to coordinate the biogenesis and turnover of mitochondria. Uncoupling of these two processes during ageing contributes to overproliferation of damaged mitochondria and decline of cellular function.

PMID:
25896323
DOI:
10.1038/nature14300
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group
Loading ...
Support Center