Mitochondrial acyl carrier protein (ACP) at the interface of metabolic state sensing and mitochondrial function

Abstract Acyl carrier protein(ACP) is a principal partner in the cytosolic and mitochondrial fatty acid synthesis (FAS) pathways. The active form holo-ACP serves as FAS platform, using its 4′- phosphopantetheinegroup to present covalently attached FAS intermediates to the enzymes responsible for the acylchain elongation process. Mitochondrial unacylated holo-ACP is a component of mammalian mitoribosomes, and acylatedACP species participate as interaction partners in several ACP-LYRM (leucine-tyrosine-arginine motif)-protein heterodimers that act either as assembly factors or subunits of the electron transport chainand Fe-S cluster assembly complexes. Moreover, octanoyl-ACP provides the C8 backbone for endogenous lipoic acidsynthesis. Accumulating evidence suggests that mtFAS-generated acyl-ACPs act as signaling molecules in an intramitochondrial metabolic state sensing circuit, coordinating mitochondrial acetyl-CoAlevels with mitochondrial respiration, Fe-S cluster biogenesis and protein lipoylation.