Complex I assembly factor ACAD9, mitochondrial (ACAD9)

Complex I assembly factor ACAD9, mitochondrial (ACAD9), is a mitochondrial enzyme that serves dual roles in human cells: it is essential for the assembly of respiratory chain Complex I and also displays enzymatic activity in long-chain fatty acid β-oxidation, particularly in tissues with high ACAD9 expression such as the brain and liver[2][3][5][6][7][8]. Functionally, ACAD9 participates in forming part of the MCIA complex, cooperating with NDUFAF1 and ECSIT to facilitate the proper biogenesis and stability of Complex I, which is critical for oxidative phosphorylation and cellular energy production[1][2][4][6][7]. Pathogenic variants in *ACAD9* are associated with a spectrum of mitochondrial disorders, including complex I deficiency that can result in cardiomyopathy, encephalomyopathy, exercise intolerance, muscle weakness, and other multi-organ symptoms, depending on the tissues affected and residual enzyme activity[4][5][6][8]. Riboflavin supplementation has been used to support cellular function in some ACAD9-related deficiencies, presumably by enhancing residual enzyme activity through increased FAD availability[4][5]. ACAD9 deficiency diagnosis often leverages biochemical markers such as complex I activity and the acylcarnitine profile, with genetic testing confirming pathogenic variants in the *ACAD9* gene[3][4][8].

Other names

Acyl-CoA dehydrogenase family member 9MC1DN20NPD002MGC14452ACAD-9very-long-chain acyl-CoA dehydrogenaseacyl-Coenzyme A dehydrogenase family member 9

Riboflavin acts as a precursor for FAD, potentially supporting residual enzymatic activity when ACAD9 is mutated or deficient[4][5]