The emerging, multifaceted role of mitophagy in cancer and cancer therapeutics

Panigrahi, Debasna Pritimanjari; Praharaj, Prakash Priyadarshi; Bhol, Chandra Sekhar; Mahapatra, Kewal Kumar; Patra, Srimanta; Behera, Bishnu Prasad; Mishra, Soumya Ranjan; Bhutia, Sujit K.

doi:10.1016/j.semcancer.2019.07.015

Cited by 178 publications

(144 citation statements)

References 177 publications

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“…As an evolutionarily conserved cellular process, mitophagy selectively eliminates dysfunctional mitochondria by directing them to the autophagosome and degrading them. However, when mitophagy is dysregulated, mitochondria are damaged and accumulate, causing carcinogenesis and cancer progression (36). PINK1 does not affect the mitophagy process directly (37).…”

Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Zhu

Jiang

et al. 2020

Front. Oncol.

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Section: Discussionmentioning

confidence: 99%

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Zhu

Jiang

et al. 2020

Front. Oncol.

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“…TFAM and PGC-1α have not yet been linked to radioresistance, but Wang et al (2017) recently showed that silencing mitochondrial single stranded DNA-binding protein (SSBP1), a protein that normally ensures mtDNA stability, decreased mtDNA copy number and sensitized H1299 human lung cancer cells to X-ray irradiation. If acquired radioresistance would rely on optimized mitochondrial dynamics, then it could potentially be reversed by targeting mitophagy (Panigrahi et al, 2019) and/or mitochondrial biogenesis (Wang et al, 2016) in cancer cells. Alternative hypotheses connecting mitochondria to radioresistance would involve differences in calcium transport and release and mitochondrial resistance to apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells

et al. 2020

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The clinical management of head and neck squamous cell carcinoma (HNSCC) commonly involves chemoradiotherapy, but recurrences often occur that are associated with radioresistance. Using human SQD9 laryngeal squamous cell carcinoma cancer cells as a model, we aimed to identify metabolic changes associated with acquired radioresistance. In a top-down approach, matched radiosensitive and radioresistant SQD9 cells were generated and metabolically compared, focusing on glycolysis, oxidative phosphorylation (OXPHOS) and ROS production. The cell cycle, clonogenicity, tumor growth in mice and DNA damage-repair were assessed. Mitochondrial DNA (mtDNA) was sequenced. In a bottom-up approach, matched glycolytic and oxidative SQD9 cells were generated using FACS-sorting, and tested for their radiosensitivity/radioresistance. We found that acquired radioresistance is associated with a shift from a glycolytic to a more oxidative metabolism in SQD9 cells. The opposite was also true, as the most oxidative fraction isolated from SQD9 wild-type cells was also more radioresistant than the most glycolytic fraction. However, neither reduced hexokinase expression nor OXPHOS were directly responsible for the radioresistant phenotype. Radiosensitive and radioresistant cells had similar proliferation rates and were equally efficient for ATP production. They were equally sensitive to redox stress and had similar DNA damage repair, but radioresistant cells had an increased number of mitochondria and a higher mtDNA content. Thus, an oxidative switch is associated with but is not responsible for acquired radioresistance in human SQD9 cells. In radioresistant cells, more abundant and fitter mitochondria could help to preserve mitochondrial functions upon irradiation.

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“…Similarly, dysfunctional mitophagy is a characteristic phenomenon of cancer. Most mitophagy receptors or regulators are involved in cancer; however, whether they act as tumor promoters or tumor suppressors seems to be highly dependent on tumor type and TME (Table 1), which is described below (Panigrahi et al, 2019;Praharaj et al, 2019;Vara-Perez et al, 2019;Ferro et al, 2020).…”

Section: Mitophagy In Cancermentioning

confidence: 99%

Mitophagy Receptors in Tumor Biology

Xie

Liu

Kang

et al. 2020

Front. Cell Dev. Biol.

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Mitochondria are multifunctional organelles that regulate cancer biology by synthesizing macromolecules, producing energy, and regulating cell death. The understanding of mitochondrial morphology, function, biogenesis, fission and fusion kinetics, and degradation is important for the development of new anticancer strategies. Mitophagy is a type of selective autophagy that can degrade damaged mitochondria under various environmental stresses, especially oxidative damage and hypoxia. The key regulator of mitophagy is the autophagy receptor, which recognizes damaged mitochondria and allows them to enter autophagosomes by binding to MAP1LC3 or GABARAP, and then undergo lysosomal-dependent degradation. Many components of mitochondria, including mitochondrial membrane proteins (e.g., PINK1, BNIP3L, BNIP3, FUNDC1, NIPSNAP1, NIPSNAP2, BCL2L13, PHB2, and FKBP8) and lipids (e.g., cardiolipin and ceramides), act as mitophagy receptors in a context-dependent manner. Dysfunctional mitophagy not only inhibits, but also promotes, tumorigenesis. Similarly, mitophagy plays a dual role in chemotherapy, radiotherapy, and immunotherapy. In this review, we summarize the latest advances in the mechanisms of mitophagy and highlight the pathological role of mitophagy receptors in tumorigenesis and treatment.

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The emerging, multifaceted role of mitophagy in cancer and cancer therapeutics

Cited by 178 publications

References 177 publications

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Pan-Cancer Analysis of the Mitophagy-Related Protein PINK1 as a Biomarker for the Immunological and Prognostic Role

Fitter Mitochondria Are Associated With Radioresistance in Human Head and Neck SQD9 Cancer Cells

Mitophagy Receptors in Tumor Biology

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