Unknown

Dataset Information

0

PGC-1alpha/beta upregulation is associated with improved oxidative phosphorylation in cells harboring nonsense mtDNA mutations.


ABSTRACT: We have studied the functional effects of nonsense mitochondrial DNA (mtDNA) mutations in the COXI and ND5 genes in a colorectal tumor cell line. Surprisingly, these cells had an efficient oxidative phosphorylation (OXPHOS); however, when mitochondria from these cells were transferred to an osteosarcoma nuclear background (osteosarcoma cybrids), the rate of respiration markedly declined suggesting that the phenotypic expression of the mtDNA mutations was prevented by the colorectal tumor nuclear background. We found that there was a significant increase in the steady-state levels of PGC-1alpha and PGC-1beta transcriptional coactivators in these cells and a parallel increase in the steady-state levels of several mitochondrial proteins. Accordingly, adenoviral-mediated overexpression of PGC-1alpha and PGC-1beta in the osteosarcoma cybrids stimulated mitochondrial respiration suggesting that an upregulation of PGC-1alpha/beta coactivators can partially rescue an OXPHOS defect. In conclusion, upregulation of PGC-1alpha and PGC-1beta in the colorectal tumor cells can be part of an adaptation mechanism to help overcome the severe consequences of mtDNA mutations on OXPHOS.

SUBMITTER: Srivastava S 

PROVIDER: S-EPMC2652746 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

PGC-1alpha/beta upregulation is associated with improved oxidative phosphorylation in cells harboring nonsense mtDNA mutations.

Srivastava Sarika S   Barrett John N JN   Moraes Carlos T CT  

Human molecular genetics 20070306 8


We have studied the functional effects of nonsense mitochondrial DNA (mtDNA) mutations in the COXI and ND5 genes in a colorectal tumor cell line. Surprisingly, these cells had an efficient oxidative phosphorylation (OXPHOS); however, when mitochondria from these cells were transferred to an osteosarcoma nuclear background (osteosarcoma cybrids), the rate of respiration markedly declined suggesting that the phenotypic expression of the mtDNA mutations was prevented by the colorectal tumor nuclear  ...[more]

Similar Datasets

| S-EPMC2932777 | biostudies-literature
| S-EPMC404086 | biostudies-other
| S-EPMC2778471 | biostudies-literature
2013-07-26 | GSE23242 | GEO
| S-EPMC2682896 | biostudies-other
2010-12-01 | GSE23365 | GEO
2010-12-01 | E-GEOD-23365 | biostudies-arrayexpress
2013-07-26 | E-GEOD-23242 | biostudies-arrayexpress
| S-EPMC2804159 | biostudies-literature
| S-EPMC1622837 | biostudies-literature