IMPACT OF ACYL-CoA BINDING DOMAIN CONTAINING 3 PROTEIN (ACBD3) DEFICIENCY ON MITOCHONDRIAL ENERGY METABOLISM

A homozygous mutation c.460A>G (p.Lys154Glu) in ACBD3 gene was found by NGS in patient with mitochondrial encephalomyopathy and combined deficiency of OXPHOS complexes in muscle. ACBD3 encodes a protein localized in the Golgi apparatus and mitochondria. ACBD3 plays essential role in lipid metabolism, membrane transport, neuronal division, embryogenesis, organelle maintenance and iron homeostasis. The aims of the study were to test mitochondrial localization of ACBD3 in HEK293 and human skin fibroblast (HSF). Moreover, it was identified the impact of mutation in ACBD3 gene in patient´s samples, ACBD3 protein deficiency in HEK293 and HSF cells on biogenesis of OXPHOS complexes and mitochondrial network and ultrastructure, cholesterol distribution and Golgi apparatus structure to elucidate ACBD3 role in the pathogenesis of the patient´s phenotype. In study we confirmed association of ACBD3 with the OMM in HEK293. In contrast, ACBD3 is absent in HSF mitochondria. The stabile depletion of ACBD3 has a mild impact on levels of OXPHOS complexes in HEK293. Transient reduction of ACBD3 in HSF has any impact on mitochondrial network as well as on level of OXPHOS complex however it has marked impact on Golgi apparatus maintenance.