Upregulation of mitochondrial content in cytochrome c oxidase deficient fibroblasts

Aviram Kogot-Levin, Ann Saada, Gil Leibowitz, Devorah Soiferman, Liza Douiev, Itamar Raz, Sarah Weksler-Zangen

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Cytochrome-c-oxidase (COX) deficiency is a frequent cause of mitochondrial disease and is associated with a wide spectrum of clinical phenotypes. We studied mitochondrial function and biogenesis in fibroblasts derived from the Cohen (CDs) rat, an animal model of COX deficiency. COX activity in CDs-fibroblasts was 50% reduced compared to control rat fibroblasts (P<0.01). ROS-production in CDs fibroblasts increased, along with marked mitochondrial fragmentation and decreased mitochondrial membrane-potential, indicating mitochondrial dysfunction. Surprisingly, cellular ATP content, oxygen consumption rate (OCR) and the extracellular acidification rate (ECAR) were unchanged. To clarify the discrepancy between mitochondrial dysfunction and ATP production, we studied mitochondrial biogenesis and turnover. The content of mitochondria was higher in CDs-fibroblasts. Consistently, AMPK activity and the expression of NRF1-target genes, NRF2 and PGC1-α that mediate mitochondrial biogenesis were increased (P<0.01 vs control fibroblast). In CDs-fibrobalsts, the number of autophagosomes (LC3+ puncta) containing mitochondria in CDs fibroblasts was similar to that in control fibroblasts, suggesting that mitophagy was intact. Altogether, our findings demonstrate that mitochondrial dysfunction and oxidative stress are associated with an increase in mitochondrial biogenesis, resulting in preservation of ATP generation.

Original languageAmerican English
Article numbere0165417
JournalPLoS ONE
Volume11
Issue number10
DOIs
StatePublished - Oct 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Kogot-Levin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Fingerprint

Dive into the research topics of 'Upregulation of mitochondrial content in cytochrome c oxidase deficient fibroblasts'. Together they form a unique fingerprint.

Cite this