| General information | Literature | Expression | Regulation | Mutation | Homolog | Interaction |
Basic Information | |
|---|---|
Gene ID | 4535 |
Name | ND1 |
Synonymous | NADH dehydrogenase, subunit 1 (complex I);MT-ND1;mitochondrially encoded NADH dehydrogenase 1 |
Definition | NADH dehydrogenase subunit 1 |
Position | - |
Gene type | protein-coding |
Title | Abstract |
| miscellaneous | The oncogenic versus suppressor roles of mitochondrial genes have long been debated. Peculiar features of mitochondrial genetics such as hetero/homoplasmy and mutation threshold are seldom taken into account in this debate. Mitochondrial DNA (mtDNA) mutations generally have been claimed to be protumorigenic, but they are also hallmarks of mostly benign oncocytic tumors wherein they help reduce adaptation to hypoxia by destabilizing hypoxia-inducible factor-1alpha (HIF1alpha). To determine the influence of a disassembling mtDNA mutation and its hetero/homoplasmy on tumorigenic and metastatic potential, we injected mice with tumor cells harboring different loads of the gene MTND1 m.3571insC. Cell cultures obtained from tumor xenografts were then analyzed to correlate energetic competence, apoptosis, alpha-ketoglutarate (alpha-KG)/succinate (SA) ratio, and HIF1alpha stabilization with the mutation load. A threshold level for the antitumorigenic effect of MTND1 m.3571insC mutation was defined, above which tumor growth and invasiveness were reduced significantly. Notably, HIF1alpha destabilization and downregulation of HIF1alpha-dependent genes occurred in cells and tumors lacking complex I (CI), where there was an associated imbalance of alpha-KG/SA despite the presence of an actual hypoxic environment. These results strongly implicate mtDNA mutations as a cause of oncocytic transformation. Thus, the antitumorigenic and antimetastatic effects of high loads of MTND1 m.3571insC, following |