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

Alfonso Schiavi, Alessandro Torgovnick, Alison Kell, Evgenia Megalou, Natascha Castelein, Ilaria Guccini, Laura Marzocchella, Sara Gelino, Malene Hansen, Florence Malisan, Ivano Condò, Roberto Bei, Shane L. Rea, Bart P. Braeckman, Nektarios Tavernarakis, Roberto Testi, Natascia Ventura

Research output: Contribution to journalArticle

38 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)191-201
Number of pages11
JournalExperimental Gerontology
Volume48
Issue number2
DOIs
StatePublished - Feb 2013

Fingerprint

Autophagy
Lipids
Friedreich Ataxia
Caenorhabditis elegans
Mitochondria
Animals
Mitochondrial Proteins
p53 Genes
Sensory Receptor Cells
frataxin
Lipid Metabolism
Neurons
Genes
Proteins

Keywords

  • Aging
  • Autophagy
  • Fat
  • Frataxin
  • Mitochondria
  • Nematode
  • P53/cep-1

ASJC Scopus subject areas

  • Aging
  • Biochemistry
  • Cell Biology
  • Endocrinology
  • Genetics
  • Molecular Biology

Cite this

Schiavi, A., Torgovnick, A., Kell, A., Megalou, E., Castelein, N., Guccini, I., ... Ventura, N. (2013). Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. Experimental Gerontology, 48(2), 191-201. https://doi.org/10.1016/j.exger.2012.12.002

Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. / Schiavi, Alfonso; Torgovnick, Alessandro; Kell, Alison; Megalou, Evgenia; Castelein, Natascha; Guccini, Ilaria; Marzocchella, Laura; Gelino, Sara; Hansen, Malene; Malisan, Florence; Condò, Ivano; Bei, Roberto; Rea, Shane L.; Braeckman, Bart P.; Tavernarakis, Nektarios; Testi, Roberto; Ventura, Natascia.

In: Experimental Gerontology, Vol. 48, No. 2, 02.2013, p. 191-201.

Research output: Contribution to journalArticle

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 2013, 'Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans', Experimental Gerontology, vol. 48, no. 2, pp. 191-201. https://doi.org/10.1016/j.exger.2012.12.002
Schiavi, Alfonso ; Torgovnick, Alessandro ; Kell, Alison ; Megalou, Evgenia ; Castelein, Natascha ; Guccini, Ilaria ; Marzocchella, Laura ; Gelino, Sara ; Hansen, Malene ; Malisan, Florence ; Condò, Ivano ; Bei, Roberto ; Rea, Shane L. ; Braeckman, Bart P. ; Tavernarakis, Nektarios ; Testi, Roberto ; Ventura, Natascia. / Autophagy induction extends lifespan and reduces lipid content in response to frataxin silencing in C. elegans. In: Experimental Gerontology. 2013 ; Vol. 48, No. 2. pp. 191-201.
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