COX17 acetylation via MOF–KANSL complex promotes mitochondrial integrity and function

• DOI: 10.1038/s42255-023-00904-w
• Publication Date: 2023-10-09T16:01:56Z
• Authors: Sukanya Guhathakurta; Niyazi Umut Erdogdu; Juliane J. Hoffmann; Iga Grzadzielewska; Alexander Schendz...; Janine Seyfferth; Christoph U. Mårt...; Mauro Corrado; Adam Karoutas; Bettina Warscheid; Nikolaus Pfanner; Thomas Becker; Asifa Akhtar
• Keywords: Mitochondrial respiratory chain

Abstract Reversible acetylation of mitochondrial proteins is a regulatory mechanism central to adaptive metabolic responses. Yet, how such functionally relevant protein achieved remains unexplored. Here we reveal an unprecedented role the MYST family lysine acetyltransferase MOF in energy metabolism via acetylation. Loss MOF–KANSL complex members leads defects including fragmentation, reduced cristae density and impaired electron transport chain IV integrity primary mouse embryonic fibroblasts. We demonstrate COX17, assembly factor, as bona fide target MOF. COX17 or expression its non-acetylatable mutant phenocopies observed upon depletion. The acetylation-mimetic rescues these maintains activity even absence MOF, suggesting activatory Fibroblasts from patients with syndrome who have intellectual disability also revealed respiratory that could be restored by alternative oxidase, mitochondrially targeted Overall, our findings highlight critical physiology provide new insights into syndrome.