RRC ID 45623
著者 Palikaras K, Lionaki E, Tavernarakis N.
タイトル Coordination of mitophagy and mitochondrial biogenesis during ageing in C. elegans.
ジャーナル Nature
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.
巻・号 521(7553)
ページ 525-8
公開日 2015-5-28
DOI 10.1038/nature14300
PII nature14300
PMID 25896323
MeSH Aging / pathology Aging / physiology* Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / metabolism Carrier Proteins DNA-Binding Proteins / metabolism Homeostasis Insulin / metabolism Insulin-Like Growth Factor I / metabolism Longevity Membrane Proteins / metabolism Mitochondria / genetics Mitochondria / metabolism* Mitochondria / pathology Mitophagy* / genetics Signal Transduction Stress, Physiological Transcription Factors / metabolism
IF 42.779
引用数 257
WOS 分野 CELL BIOLOGY
リソース情報
線虫 tm376 tm1779