Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans.

Experimental gerontology | Feb 28, 2013

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C. elegans, while its partial deficiency extends animal lifespan in a p53 dependent manner. In this paper we provide further insight into frataxin control of C. elegans longevity by showing that a substantial reduction of frataxin protein expression is required to extend lifespan, affect sensory neurons functionality, remodel lipid metabolism and trigger autophagy. We find that Beclin and p53 genes are required to induce autophagy and concurrently reduce lipid storages and extend animal lifespan in response to frataxin suppression. Reciprocally, frataxin expression modulates autophagy in the absence of p53. Human Friedreich ataxia-derived lymphoblasts also display increased autophagy, indicating an evolutionarily conserved response to reduced frataxin expression. In sum, we demonstrate a causal connection between induction of autophagy and lifespan extension following reduced frataxin expression, thus providing the rationale for investigating autophagy in the pathogenesis and treatment of Friedreich's ataxia and possibly other human mitochondria-associated disorders.

Pubmed ID: 23247094 RIS Download

Mesh terms: AMP-Activated Protein Kinases | Animals | Apoptosis Regulatory Proteins | Autophagy | Caenorhabditis elegans | Caenorhabditis elegans Proteins | Friedreich Ataxia | Gene Silencing | Humans | Iron-Binding Proteins | Lipid Metabolism | Longevity | Mitochondria | RNA Interference | Sensory Receptor Cells | Tumor Suppressor Protein p53

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: Telethon, Id: GGP11102
  • Agency: NIA NIH HHS, Id: R01 AG038664
  • Agency: NIA NIH HHS, Id: R01 AG039756

WormBase (Data, Gene Expression)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.