Baechler, SA;
Dalla Rosa, I;
Spinazzola, A;
Pommier, Y;
(2019)
Beyond the unwinding: Role of TOP1MT in mitochondrial translation.
Cell Cycle
, 18
(19)
pp. 2377-2384.
10.1080/15384101.2019.1646563.
Preview |
Text
29_07_2019_Beyond the.pdf - Accepted Version Download (1MB) | Preview |
Abstract
Mitochondria contain their own genome (mtDNA), encoding 13 proteins of the enzyme complexes of the oxidative phosphorylation. Synthesis of these 13 mitochondrial proteins requires a specific translation machinery, the mitoribosomes whose RNA components are encoded by the mtDNA, whereas more than 80 proteins are encoded by nuclear genes. It has been well established that mitochondrial topoisomerase I (TOP1MT) is important for mtDNA integrity and mitochondrial transcription as it prevents excessive mtDNA negative supercoiling and releases topological stress during mtDNA replication and transcription. We recently showed that TOP1MT also supports mitochondrial protein synthesis, and thus is critical for promoting tumor growth. Impaired mitochondrial protein synthesis leads to activation of the mitonuclear stress response through the transcription factor ATF4, and induces cytoprotective genes in order to prevent mitochondrial and cellular dysfunction. In this perspective, we highlight the novel role of TOP1MT in mitochondrial protein synthesis and as potential target for chemotherapy.
Archive Staff Only
 |
View Item |
