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MitoSafe hypothesis: safeguarding mitochondrial morphology and innate immunity
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DOI：10.1016/j.tcb.2026.04.007.png)
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Abstract
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Cells sense mitochondrial size and suppress mitochondrial fusion when mitochondria become hyperfused through the MitoSafe mechanism. MitoSafe acts by inhibiting outer membrane fusion through decreased mitofusin 1 levels and inner membrane fusion via OPA1 cleavage. In vivo, MitoSafe regulates mitochondrial morphology through Parkin and OMA1 in the absence of overt mitochondrial stress. Loss of MitoSafe leads to the release of mitochondrial DNA and the activation of innate immunity in vivo.
Keywords:
MitoSafe
mitochondrial fusion
mitofusin 1
OPA1
innate immunity
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