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

• Published in: Biochimica et biophysica acta. Molecular cell research 2019-12, Vol.1866 (12), p.118540-118540, Article 118540
• Main Authors: Masud, Ali J., Kastaniotis, Alexander J., Rahman, M. Tanvir, Autio, Kaija J., Hiltunen, J. Kalervo
• Format: Article
• Language: English
• Subjects: Acetyl Coenzyme A - metabolism; ACP; Acyl Carrier Protein - genetics; Acyl Carrier Protein - metabolism; Amino Acid Sequence; Animals; Fe-S cluster; Humans; Lipids; Lipoic acid; LYRM proteins; Mitochondria - metabolism; Mitochondrial FAS; Mitochondrial respiratory chain; Mitoribosome; Regulation; Sequence Alignment
• ISSN: 0167-4889; 1879-2596
• DOI: 10.1016/j.bbamcr.2019.118540

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′-phosphopantetheine group to present covalently attached FAS intermediates to the enzymes responsible for the acyl chain elongation process. Mitochondrial unacylated holo-ACP is a component of mammalian mitoribosomes, and acylated ACP 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 chain and Fe-S cluster assembly complexes. Moreover, octanoyl-ACP provides the C8 backbone for endogenous lipoic acid synthesis. Accumulating evidence suggests that mtFAS-generated acyl-ACPs act as signaling molecules in an intramitochondrial metabolic state sensing circuit, coordinating mitochondrial acetyl-CoA levels with mitochondrial respiration, Fe-S cluster biogenesis and protein lipoylation. •Eukaryotic mitochondria have a full set of discrete enzymes for de novo synthesis of fatty acid in an ACP-dependent manner.•MtACP interacts with complex I, assembly components of respiratory complexes, mitoribosomes and the Fe-S cluster synthesis.•Most of these interactions are transmitted through proteins of the leucine-tyrosine-arginine motif (LYRM) family.•MtFAS-generated acyl-ACPs act as signaling molecules at the interface of mitochondrial metabolic state and respiration.