Disruption of mitochondrial functions and oxidative stress contribute to neurologic dysfunction in organic acidurias.

Disruption of mitochondrial functions and oxidative stress contribute to neurologic dysfunction in organic acidurias. Arch Biochem Biophys. 2020 Oct 21;:108646 Authors: Wajner M, Vargas CR, Amaral AU Abstract Organic acidurias (OADs) are inherited disorders of amino acid metabolism biochemically characterized by accumulation of short-chain carboxylic acids in tissues and biological fluids of the affected patients and clinically by predominant neurological manifestations. Some of these disorders are amenable to treatment, which significantly decreases mortality and morbidity, but it is still ineffective to prevent long-term neurologic and systemic complications. Although pathogenesis of OADs is still poorly established, recent human and animal data, such as lactic acidosis, mitochondrial morphological alterations, decreased activities of respiratory chain complexes and altered parameters of oxidative stress, found in tissues from patients and from genetic mice models with these diseases indicate that disruption of critical mitochondrial functions and oxidative stress play an important role in their pathophysiology. Furthermore, organic acids that accumulate in the most prevalent OADs were shown to compromise bioenergetics, by decreasing ATP synthesis, mitochondrial membrane potential, reducing equivalent content and calcium retention capacity, besides inducing mitochondrial swelling, reactive oxygen and nitrogen species generation and...
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research