Mouse anti-Human/Mouse/Rat sapiens (Human) ACAD9 Monoclonal Antibody

Function

Together with NDUFAF1 and ECSIT, forms part of the mitochondrial complex I (MCIA),which is required for the biogenesis of respiratory Complex I (CI) and is therefore crucial for the activation of the oxidative phosphorylation system (PubMed:20816094, PubMed:24158852, PubMed:32320651, PubMed:38086790). ECSIT binding triggers a large conformational change, switching ACAD9 from a fatty acid oxidation (FAO) enzyme to a CI assembly factor (PubMed:38086790). The function in CI assembly is independent of the fatty acid oxidation (FAO) activity of the protein (PubMed:24158852). As FAO enzyme, it catalyzes the first step in mitochondrial FAO, which consists in the proR-proR stereospecific alpha, beta-dehydrogenation of fatty acyl-CoA thioesters using the electron transfer flavoprotein (ETF) as their physiologic electron acceptor, resulting in the formation of trans-2-enoyl-CoA ((2E)-enoyl-CoA) (PubMed:12359260, PubMed:16020546, PubMed:17564966, PubMed:21237683, PubMed:24158852). Its preferred substrates are both saturated and unsaturated long-chain acyl-CoA substrates, with optimum activity toward the latter (PubMed:12359260, PubMed:16020546, PubMed:17564966, PubMed:21237683, PubMed:24158852). In addition, based on its established catalytic mechanism, and combined genetic interaction or mutant phenotype evidence, it is predicted to act also on substrates that have not been tested experimentally but are metabolized by mitochondrial FAO, including long-chain unsaturated fatty acids such as linoleate (9Z,12Z-octadecadienoate), linolenate (9Z,12Z,15Z-octadecatrienoate), and others (PubMed:26474213). Among the different mitochondrial acyl-CoA dehydrogenases, its FAO activity overlaps with that of ACADV and ACADL, but plays a primary role in tissues where it is the main long-chain ACAD expressed, such as the central nervous system (PubMed:16020546, PubMed:17564966, PubMed:24158852, PubMed:25721401, PubMed:26474213). It differs significantly from ACADVL in the use of polyunsaturated substrates in vitro, especially docosahexaenoic acid (which is not primarily used for energy but mainly beta-oxidized in the peroxisomes) (PubMed:16020546, PubMed:17564966)

Subcellular Location

Mitochondrion inner membrane (Peripheral membrane protein)

Disease Association

Mitochondrial complex I deficiency, nuclear type 20 (MC1DN20) : An autosomal recessive metabolic disorder associated with mitochondrial complex I deficiency, resulting in multisystemic and variable manifestations. Clinical features include infantile onset of acute metabolic acidosis, Reye-like episodes (brain edema and vomiting that may rapidly progress to seizures, coma and death), exercise intolerance, hypertrophic cardiomyopathy, liver failure, muscle weakness, and neurologic dysfunction. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Ubiquitously expressed in most normal human tissues and cancer cell lines with higher levels in heart, skeletal muscles, and the central nervous system (where it is the highest expressed ACAD) (PubMed:12359260, PubMed:17564966). Highly expressed (at protein level) in the cerebellum (Purkinje neurons, dentate nucleus, and in the granular layer), where ACADV is not found (PubMed:17564966, PubMed:21237683)

Subunit

Homodimer (PubMed:16020546). Interacts with NDUFAF1 and ECSIT (PubMed:20816094). Part of the mitochondrial complex I assembly/MCIA complex that comprises at least the core subunits TMEM126B, NDUFAF1, ECSIT and ACAD9 and complement subunits such as COA1 and TMEM186 (PubMed:32320651). Interacts with TMEM70 and TMEM242 (PubMed:33753518)

• Zhang J. et al. Cloning and functional characterization of ACAD-9, a novel member of human acyl-CoA dehydrogenase family. — Biochem. Biophys. Res. Commun. (2002)
• Ota T. et al. Complete sequencing and characterization of 21,243 full-length human cDNAs. — Nat. Genet. (2004)
• Mural R.J. et al. PubMed: CI-5GBD0VIIJ7C63 (SEP-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Ensenauer R. et al. Human acyl-CoA dehydrogenase-9 plays a novel role in the mitochondrial beta-oxidation of unsaturated fatty acids. — J. Biol. Chem. (2005)
• He M. et al. A new genetic disorder in mitochondrial fatty acid beta-oxidation: ACAD9 deficiency. — Am. J. Hum. Genet. (2007)
• Choudhary C. et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. — Science (2009)
• Nouws J. et al. Acyl-CoA dehydrogenase 9 is required for the biogenesis of oxidative phosphorylation complex I. — Cell Metab. (2010)