• Register
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

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice.

CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Significantly, the CISD2 gene is located on human chromosome 4q, where a genetic component for longevity maps. Here we show for the first time that CISD2 is involved in mammalian life-span control. Cisd2 deficiency in mice causes mitochondrial breakdown and dysfunction accompanied by autophagic cell death, and these events precede the two earliest manifestations of nerve and muscle degeneration; together, they lead to a panel of phenotypic features suggestive of premature aging. Our study also reveals that Cisd2 is primarily localized in the mitochondria and that mitochondrial degeneration appears to have a direct phenotypic consequence that triggers the accelerated aging process in Cisd2 knockout mice; furthermore, mitochondrial degeneration exacerbates with age, and the autophagy increases in parallel to the development of the premature aging phenotype. Additionally, our Cisd2 knockout mouse work provides strong evidence supporting an earlier clinical hypothesis that WFS is in part a mitochondria-mediated disorder; specifically, we propose that mutation of CISD2 causes the mitochondria-mediated disorder WFS2 in humans. Thus, this mutant mouse provides an animal model for mechanistic investigation of Cisd2 protein function and help with a pathophysiological understanding of WFS2.

Pubmed ID: 19451219

Authors

  • Chen YF
  • Kao CH
  • Chen YT
  • Wang CH
  • Wu CY
  • Tsai CY
  • Liu FC
  • Yang CW
  • Wei YH
  • Hsu MT
  • Tsai SF
  • Tsai TF

Journal

Genes & development

Publication Data

May 15, 2009

Associated Grants

None

Mesh Terms

  • Aging
  • Aging, Premature
  • Animals
  • Autophagy
  • Carrier Proteins
  • Disease Models, Animal
  • Female
  • Glucose Intolerance
  • Humans
  • Longevity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mitochondria
  • Mitochondrial Proteins
  • Muscles
  • Nerve Tissue Proteins
  • Neurons
  • Optic Nerve Diseases
  • Wolfram Syndrome