Take our Survey

Reference: Sharma LK, et al. (2011) Mitochondrial respiratory complex I dysfunction promotes tumorigenesis through ROS alteration and AKT activation. Hum Mol Genet 20(23):4605-16

Reference Help

Abstract


Previously, we have shown that a heteroplasmic mutation in mitochondrial DNA-encoded complex I ND5 subunit gene resulted in an enhanced tumorigenesis through increased resistance to apoptosis. Here we report that the tumorigenic phenotype associated with complex I dysfunction could be reversed by introducing a yeast NADH quinone oxidoreductase (NDI1) gene. The NDI1 mediated electron transfer from NADH to Co-Q, bypassed the defective complex I and restored oxidative phosphorylation in the host cells. Alternatively, suppression of complex I activity by a specific inhibitor, rotenone or induction of oxidative stress by paraquat led to an increase in the phosphorylation of v-AKT murine thymoma viral oncogene (AKT) and enhanced the tumorigenesis. On the other hand, antioxidant treatment can ameliorate the reactive oxygen species-mediated AKT activation and reverse the tumorigenicity of complex I-deficient cells. Our results suggest that complex I defects could promote tumorigenesis through induction of oxidative stress and activation of AKT pathway.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't | Research Support, N.I.H., Extramural
Authors
Sharma LK, Fang H, Liu J, Vartak R, Deng J, Bai Y
Primary Lit For
Additional Lit For
Review For

Interaction Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Type Assay Annotation Action Modification Phenotype Source Reference

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Gene Ontology Term Qualifier Aspect Method Evidence Source Assigned On Annotation Extension Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, SPELL, or YeastMine.

Regulator Target Experiment Assay Construct Conditions Strain Background Reference