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Respiratory Complex I dysfunction in cancer: from a maze of cellular adaptive responses to potential therapeutic strategies
Author(s) -
Sollazzo Manuela,
De Luise Monica,
Lemma Silvia,
Bressi Licia,
Iorio Maria,
Miglietta Stefano,
Milioni Sara,
Kurelac Ivana,
Iommarini Luisa,
Gasparre Giuseppe,
Porcelli Anna Maria
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.16218
Subject(s) - reprogramming , bioenergetics , tumor microenvironment , mitochondrion , carcinogenesis , biology , cancer cell , cancer , phenotype , microbiology and biotechnology , cell , cancer research , neuroscience , gene , genetics
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.