Pleiotropic regulation of mitochondrial translational factors in governing proliferation, apoptosis and metastasis during cancer progression

Mitochondrial translation relies on the coordinated activity of mitoribosomes, mitochondrial ribosome proteins, mitochondria-specific transfer RNAs, and dedicated translation factors, including mitochondrial initiation factor 2/3, mitochondrial elongation factor Tu, mitochondrial elongation factor Ts, mitochondrial elongation factor G1/G2, mitochondrial elongation factor 4, mitochondrial ribosome recycling factor, and mitochondrial release factor 1A. These components collectively drive the synthesis of 13 essential polypeptides encoded by mitochondrial DNA, all constituting subunits of the oxidative phosphorylation complexes. Although mitochondrial metabolism is increasingly recognized as a key player in cancer, the specific contribution of mitochondrial translation to cancer progression remains poorly explored. This gap in knowledge limits our understanding of how mitochondrial dysfunction contributes to tumor initiation, progression, and therapy resistance. Herein, in this review, we highlight how dysregulation of mitochondrial translation factors can influence major cancer hallmarks such as sustained proliferative signaling, resistance to apoptosis, and increased invasion and metastasis. In addition, we discuss the known molecular mechanisms that link defects in mitochondrial translation to oncogenic features. We also consolidate current insights into the mitochondrial translation machinery and discuss recent evidence of its role in cancer, aiming to emphasize mitochondrial translation as a contributor to malignancy and a potential therapeutic target.