Dear Jose,

mitophagy modulation seems to be a promising strategy for cancer treatment. Please consult the literature in the attachment for more details.

Cheers, Christian

Article Salinomycin induces activation of autophagy, mitophagy and a...

Article Mitochondrial Dysfunction in Cancer

Article Mitophagy and cancer

Yes, it is crucial in maintaining the mitochondrial number in tumor cells. In other words, the mitophagy is an important process in mitochondrial dynamic. 

Yes and advise you to read this interesting paper on mitophagy to really understand it's importance 

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4373087/

Mitophagy is a process in which old and dysfunctional mitochondria undergoes p62-dependent autophagic degradation. Cancer cells generally accumulate unfolded-protein response (UPR) stress and mitophagy is promoted in malignant cells. When mitophagy is blocked, enhanced UPR signaling pathway and impaired mitochondrial metabolism induce the failure for cancer cells to continue to proliferate and survive.

http://jeccr.biomedcentral.com/articles/10.1186/s13046-015-0221-y

Mitophagy is a selective form of macro-autophagy in which mitochondria are selectively targeted for degradation in autophagolysosomes. Mitophagy can have the beneficial effect of eliminating old and/or damaged mitochondria, thus maintaining the integrity of the mitochondrial pool. However, mitophagy is not only limited to the turnover of dysfunctional mitochondria but also promotes reduction of overall mitochondrial mass in response to certain stresses, such as hypoxia and nutrient starvation. This prevents generation of reactive oxygen species and conserves valuable nutrients (such as oxygen) from being consumed inefficiently, thereby promoting cellular survival under conditions of energetic stress. The failure to properly modulate mitochondrial turnover in response to oncogenic stresses has been implicated both positively and negatively in tumorigenesis, while the potential of targeting mitophagy specifically as opposed to autophagy in general as a therapeutic strategy remains to be explored. Here is an interesting review

Yes I concur with the group very important in developing more effective therapies to treat Cancer.

Hello Jose,

So there was a interesting article published recently in Science. In brief what the authors demonstrate that cardiac cells undergo mitophagy to switch from regular glucose based mitochondrial metabolism to adult tissue where mitochondrial metabolism is exclusively based on fatty acid oxidation. Since the crystalline structure of mitochondria is rigid it is not flexible to shift easily from one metabolite to another. It will have to destroy old mitochondria and generate new mitochondria.

If you apply this scenario to cancer cells, it will be obvious that most cancer cells might have to go through mitophagy to shift from the baseline mitochondrial metabolism to new metabolism driving cancer growth,whatever it may be. In this scenario, treating cancers will have to be two pronged approach- 1. Inhibit mitophagy to inhibit cancer cells from adapting to new metabolism 2. Inhibit mitochondrial biogenesis to prevent generating new mitochondria. 

Both the approaches would then have to be targeted specifically to cancer cells in order to achieve therapy. 

https://www.sciencemag.org/content/350/6265/aad2459.abstract

I disagree with Suresh, Mitochondria are damaged in most cancers and cancer growth relies mainly on glycolysis.

Thank you Dr. Gonzalez for your answer. But, I respectfully disagree with you as well. Although glycolysis is the main thrust of many labs working on cancer cell metabolism, it is unfortunately not the only source of energy of cancer cells. Please look at the review articles.Also please look at Nature article from Dr. Nissim Hay's lab.

http://www.cell.com/cell-metabolism/abstract/S1550-4131(13)00207-6

http://www.ncbi.nlm.nih.gov/pubmed/22660331

http://www.ncbi.nlm.nih.gov/pubmed/21508971/

Dear Suresh "  If everybody is thinking alike then no one is thinking" Ben Franklin. Thanks for the articles.Cancer cells also use glutamine.

Please read the following:

https://www.researchgate.net/publication/229325765_The_bio-energetic_theory_of_carcinogenesis

http://download.springer.com/static/pdf/494/art%253A10.1186%252F1743-7075-7-7.pdf?originUrl=http%3A%2F%2Fnutritionandmetabolism.biomedcentral.com%2Farticle%2F10.1186%2F1743-7075-7-7&token2=exp=1451718838~acl=%2Fstatic%2Fpdf%2F494%2Fart%25253A10.1186%25252F1743-7075-7-7.pdf*~hmac=ff3f4ffa09bbbf548e7d33d7980e9d3b7b13e2b57d817ccf7936bf81d79af57b

Happy New Year! Please keep in touch!

Article The bio-energetic theory of carcinogenesis

Thank you everyone!

These are great explanations! I dont know if its helpful but if you want to see how we think mitophagy may be executed as it relates to breast cancer and the UPR, you could take a look at this small study (it might have some useful citations to the literature if nothing else); Cook et al., Cell Biosci 4: 16 (doi: 10.1186/2045-3701-4-16), 2014. I think its uploaded to ResearchGate but I can send it to you if you want to read it. We think that the selective regulation of autophagic processes (including mitophagy) are critical in restoring metabolic homeostasis in the face of the stresses of endocrine therapies and so offer multiple potential targets for therapeutic intervention. I think its reasonable to speculate that, since the UPR and autophagy represent a fairly ancient integrated mechanism for addressing stress, responsiveness to many anticancer therapies that affect energy metabolism (so also  protein folding) may be affected by the ability of cells to use the UPR and autophagy (perhaps in different combinations of all of its forms) to survive. Many cell types, particularly those that normally produce/secrete large amounts of proteins, may already be "hard wired" to use this signaling when they become transformed (neoplastic). We recently reviewed these interactions from the perspective of endocrine resistance in breast cancer (Clarke et al., Mol Cell Endo, 2015 - it should also be accessible)...Bob

Thank very much, Bob

Hello Jose,

I just found an interesting article that describes the role of mitochondrial defects in cancer aetiology. Might be interesting for you because mitochondrial dysfunction is closely linked to mitophagy.

Regards, Christian

Article Defects in mitochondrial metabolism and cancer