Peroxisomal Heat Generation and Possible Relationship With Peroxisomal Disorders

Abstract

Peroxisomal disorders encompass a variety of pathologies with different clinical manifestations. X-linked adrenoleukodystrophy, an inherited neurodegenerative pathology, is characterized by mutation of a peroxisomal transport protein involved in the catabolism of very long-chain fatty acids (VLCFAs). These particular fatty acids abnormally accu-mulate in plasma and in all tissues due to the enhancement of fatty acid elongation and the impairment of fatty acid catabolism which takes place initially in the peroxisomes and afterward in the mitochondria. VLCFA accumulation cannot explain the molecular mechanisms underlying clinical manifestations in patients. Peroxisomal pathways include a product that is considered lost, but that could have a role in peroxisomal disorders: the heat produced during VLCFA catabolism. VLCFA accumulation is due to peroxisomal beta-oxidation impairment and to the enhancement of fatty acid elongation. The heat produced during peroxisomal metabolism could be a crucial factor related to the molecular mechanisms altered in X-linked adrenoleukodystrophy. VLCFA accumulation could be strongly related to the impairment of heat production, which is lost in X-linked adrenoleukodystrophy, a sort of energy necessary for the cell metabolism, which could contribute to the secondary clinical manifestations of peroxisomal disorders. Heat is not only produced during peroxisomal catabolism but also in countless metabolic pathways. It is a form of energy that could influence several parameters and could be involved in peroxisomal and metabolic disorders in general.