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Defects in the CISD2 (CDGSH iron sulfur domain 2) gene are a cause of the neurodegenerative disorder Wolfram syndrome 2. CISD2 is a zinc finger protein that localizes to the endoplasmic reticulum and mitochondria and binds an iron/sulfur cluster. CISD2 interacts with Bcl-2 and can be displaced by the BH3-only protein BIK and contributes to the regulation of BIK-initiated autophagy. CISD2 deficiency in mice causes mitochondrial breakdown accompanied by autophagic cell death as well as the development of premature aging phenotype.
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