1. Heterochromatin protein 1 regulates longevity and the mitochondrial unfolded protein response
- Author
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Cruz, Patricia de la, Heluani Gahete, Hayat, Ortega, Ángeles, Rodríguez-Palero, María Jesús, Ayuso, Cristina, Ohta, Shinya, Askjaer, Peter, Artal-Sanz, Marta, Cruz, Patricia de la, Heluani Gahete, Hayat, Ortega, Ángeles, Rodríguez-Palero, María Jesús, Ayuso, Cristina, Ohta, Shinya, Askjaer, Peter, and Artal-Sanz, Marta
- Abstract
Prohibitins (PHB) form a multimeric structure at the mitochondrial inner membrane. PHB deficiency shortens the lifespan of wild type Caenorhabditis elegans nematodes, but dramatically extends that of insulin signalling receptor (daf-2) mutants. This phenotype is accompanied by a differential induction of the mitochondrial Unfolded Protein Response (UPRmt) that is attenuated in daf-2 mutants. We identified Heterochromatin Protein Like 1 (HPL-1) as a new regulator of the UPRmt and mediator of the opposing longevity phenotype caused by PHB depletion. We report functional and structural impairments of mitochondria when HP1 is depleted from worm and human cells, showing a conservation of function. We uncovered ~70% of differently bound genes by HPL-1 upon mitochondrial stress and determined HPL-1-dependent tissue-specific alterations in gene expression in hypodermal cells. Our data shows for the first time a role for HP1 proteins in controlling gene expression in response to mitochondrial dysfunction to modulate lifespan.
- Published
- 2022