Regulation of mitochondrial fatty acid β-oxidation in human: what can we learn from inborn fatty acid β-oxidation deficiencies?

摘要: The mitochondrial fatty acid β-oxidation (FAO) pathway plays a crucial role in ATP production many tissues with high-energy demand. This is highlighted by the diverse and possibly severe clinical manifestations of inborn deficiencies. More than fifteen genetic FAO enzyme defects have been described to date, forming large group rare diseases. Inborn disorders are characterized high heterogeneity, variety gene mutations resulting complete or partial loss-of-function corresponding enzyme. panel observed phenotypes varies from multi-organ failure neonate fatal outcome, up milder late onset associated significant disabilities. Diagnosis has markedly improved over last decades, but few treatments available. clinical, biochemical, molecular analysis these provided new, sometimes unexpected, data on organization regulation humans, various tissues, at stages development. will be illustrated examples affecting enzymes long-chain import into mitochondria, Lynen helix enzymes. involvement transcriptional network regulating expression, particular PGC-1α/PPAR axis, as target for pharmacological therapy disorders, also discussed.