Genes, Volume 15, Issue 6 (June 2024) – 171 articles
Cover Story (view full-size image):
Endopeptidase CLPP and unfoldase CLPX are conserved since bacteria, as they are crucial for stress resistance and longevity. In humans, damage of mitochondria with impaired proteostasis leads to age-associated pathology and limited lifespan, with the most frequent disorder being Parkinson’s disease (PD). CLPP was implicated in PD, and it seemed easier to identify mitochondrial matrix targets of the CLPXP proteolytic machine, rather than cytosolic targets of PD-associated kinase PINK1 or ubiquitin ligase Parkin. Furthermore, CLPP-null mice have strong phenotypes including progressive neurodegeneration, while PINK1/Parkin-null mice show only discrete deficits. Neuroinflammation stood out in all three mutants, occurring early in CLPP-null mice, so its mechanism was defined in the cGAS-STING pathway. View this paper
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