Reference - Detail
| RRC ID | 46436 |
|---|---|
| Author | Schiavi A, Torgovnick A, Kell A, Megalou E, Castelein N, Guccini I, Marzocchella L, Gelino S, Hansen M, Malisan F, Condò I, Bei R, Rea SL, Braeckman BP, Tavernarakis N, Testi R, Ventura N. |
| Title | Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. |
| Journal | Exp Gerontol |
| Abstract |
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. |
| Volume | 48(2) |
| Pages | 191-201 |
| Published | 2013-2-1 |
| DOI | 10.1016/j.exger.2012.12.002 |
| PII | S0531-5565(12)00315-4 |
| PMID | 23247094 |
| PMC | PMC3572394 |
| MeSH | AMP-Activated Protein Kinases / metabolism Animals Apoptosis Regulatory Proteins / metabolism Autophagy* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Frataxin Friedreich Ataxia / genetics Friedreich Ataxia / metabolism* Friedreich Ataxia / pathology Gene Silencing* Humans Iron-Binding Proteins / genetics Iron-Binding Proteins / metabolism* Lipid Metabolism* Longevity* Mitochondria / metabolism RNA Interference Sensory Receptor Cells / metabolism Tumor Suppressor Protein p53 / metabolism |
| IF | 3.376 |
| Times Cited | 41 |
| WOS Category | GERIATRICS & GERONTOLOGY |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Blogs |
| Total number of mentions | 9 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| C.elegans | tm1944 |