Reduction of mitochondrial DNA content and respiratory chain activity occurs in adipocytes within 6-12 months of commencing nucleoside reverse transcriptase inhibitor therapy.

Abstract

Mitochondrial enzyme activity was assessed in adipocytes from seven patients initiating nucleoside reverse transcriptase inhibitor (NRTI) regimens. After 6-12 months of therapy, adipocytes from six patients demonstrated cytochrome C oxidase (COX) activity reduced from baseline, correlating positively with mitochondrial DNA levels, concomitant with evidence of cellular toxicity. Three patients also showed reduced expression of COX subunit I. This is the first study to demonstrate that NRTI-associated mtDNA depletion in adipocytes impacts functionally on mitochondrial respiratory proteins in vivo.