Project description:Mitochondria have an independent genome (mtDNA) and protein synthesis machinery that coordinately activate for mitochondrial generation. Here, we report that Krebs cycle intermediate, fumarate, connects metabolism to mitobiogenesis through binding to malic enzyme 2 (ME2). Proteomic profiling of ME2-interacting protein reveals that ME2 binds to mitoribosome proteins to regulate mitoribosome assembly and mtDNA-encoded protein production. ME2 also interacts with and modulates deoxyuridine 5-triphosphate nucleotidohydrolase activity to regulate thymidine generation and mtDNA abundance