期刊
FEBS JOURNAL
卷 289, 期 24, 页码 8003-8019出版社
WILEY
DOI: 10.1111/febs.16218
关键词
adaptive responses; cancer metabolism; mitochondria; respiratory complex I; tumor microenvironment
资金
- Associazione Italiana Ricerca sul Cancro (AIRC) [MONARCHY-IG24494, AMICO-IG22921]
- EU [722605]
- University of Bologna AlmaIdea Junior grant INTACT
- AIRC fellowship
- triennial AIRC fellowship 'Bruna Martelli'
- Universita di Bologna within the CRUI-CARE Agreement
Mitochondria play crucial roles in cellular bioenergetics and biosynthetic processes, producing signals that regulate molecular networks governing proliferation and cell death. Even in pathological contexts like tumorigenesis, mitochondrial dysfunction can confer flexibility favoring cancer cell survival. Despite initial growth delays, cancer cells with respiratory complex I impairment may adapt to resume proliferation through molecular mechanisms.
Mitochondria act as key organelles in cellular bioenergetics and biosynthetic processes producing signals that regulate different molecular networks for proliferation and cell death. This ability is also preserved in pathologic contexts such as tumorigenesis, during which bioenergetic changes and metabolic reprogramming confer flexibility favoring cancer cell survival in a hostile microenvironment. Although different studies epitomize mitochondrial dysfunction as a protumorigenic hit, genetic ablation or pharmacological inhibition of respiratory complex I causing a severe impairment is associated with a low-proliferative phenotype. In this scenario, it must be considered that despite the initial delay in growth, cancer cells may become able to resume proliferation exploiting molecular mechanisms to overcome growth arrest. Here, we highlight the current knowledge on molecular responses activated by complex I-defective cancer cells to bypass physiological control systems and to re-adapt their fitness during microenvironment changes. Such adaptive mechanisms could reveal possible novel molecular players in synthetic lethality with complex I impairment, thus providing new synergistic strategies for mitochondrial-based anticancer therapy.
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