Project description:We investigated the transcriptional response of yeast to the loss of a single copy of ARH1; an oxidoreductase of the mitochondrial inner membrane, which is among the few mitochondrial proteins that is essential for viability in yeast, ATM1; the mitochondrial inner membrane ATP-binding cassette (ABC) transporter, and of YFH1; the mitochondrial matrix iron chaperone, which oxidizes and stores iron, and interacts with Isu1p to promote Fe-S cluster assembly.
Project description:Methyltransferase MRM2 methylates the 2’-hydroxyl group of ribonucleotide U1369 of human 16S mt-rRNA. Mutations in MRM2 have been implicated in human mitochondrial-related disease. This study investigates the role of MRM2 in the biogenesis and function of human mitochondrial ribosomes. Absence of MRM2 leads to a severe defect in mitochondrial translation, with the mtLSU being trapped in immature assembly states.
Project description:Organisms respond to mitochondrial stress by activating multiple defense pathways including the mitochondrial unfolded protein response (UPRmt). However, how different layers of UPRmt regulators are orchestrated to transcriptionally activate the stress responses remains largely unknown. Here we identified CBP-1, the worm ortholog of the mammalian acetyltransferases CBP/p300, as an essential regulator for UPRmt activation, as well as for mitochondrial stress-induced immune response, amyloid-β aggregation reduction and lifespan extension in Caenorhabditis elegans. Mechanistically, CBP-1 acts downstream of histone demethylases, JMJD-1.2/JMJD-3.1, and upstream of UPRmt transcription factors including ATFS-1, to systematically induce a broad spectrum of UPRmt genes and execute multiple beneficial functions. In mouse and human populations, transcript levels of CBP/p300 positively correlate with UPRmt transcripts and longevity. Furthermore, CBP/p300 inhibition disrupts, while forced expression of p300 is sufficient to activate, the UPRmt in mammalian cells. These results highlight an evolutionarily conserved mechanism that determines mitochondrial stress response, and promotes health and longevity through CBP/p300.
