Autophagy · 2009 · 77 citations · 0 references
Life SciencesGeneticsMolecular GeneticsAgingAutophagyMitochondrial BiologyMitochondrial DiseaseMitochondrial DisordersMitochondrial DynamicsMitochondrial DysfunctionMitochondrial PhysiologyMitophagyAutophagic VacuolesMitochondrial Dysfunction In AgingMitochondrial Integrity ControlMitochondrial TurnoverMuscle Fiber DegenerationRegulation Of Mitochondrial IntegritySkeletal Muscle DegenerationWolfram Syndrome
CISD2, the causative gene for Wolfram syndrome 2 (WFS2), is a previously uncharacterized novel gene. Using a mouse genetic approach, this work demonstrated for the first time that Cisd2 is involved in mammalian life span control. Cisd2 deficiency in mice leads to mitochondrial breakdown and dysfunction; this is accompanied by cell death with autophagic features 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. This work effectively links Cisd2 gene function, mitochondrial integrity and aging in mammals.