Understanding Role of Mitophagyin Cell Survival and Cell Death in Cancer and Therapeutics

Abstract

Mitophagy is an evolutionarily conserved cellular process which selectively eliminates dysfunctional mitochondria by targeting them to the autophagosome for degradation. Dysregulated mitophagy results in the accumulation of damaged mitochondria, which plays an important role in carcinogenesis and tumor progression. Mitophagy serves to eliminate the dysfunctional mitochondria to relieve stress and tumor suppression. Our study showed that polycyclic aromatic hydrocarbons (PAHs), the constituent of cigarette smoke, vehicle exhaust, and industrial effluents induces reactive oxygen species production and apoptosis. In this connection, mitophagy induction to PAHs exposure acts as a cytoprotective response to prevent apoptosis and phytochemicals-induced mitophagy have shown potent protective effects on PAHs induced cell death and toxicity. On the otherhand, mitophagy facilitates cell survival for better adaption to aggressive tumor conditions and in response to anticancer therapy. Importantly, secretory clusterin-dependent mitophagy contributes to cell survival and chemoresistance in cancer cells. In addition, mitophagy could serve as an alternative and complementary approach to the cancer cell death mechanism for potential cancer therapy.