Dual role of mitophagy in cancer drug resistance

Abstract

The effectiveness of chemotherapy is largely limited by drug resistance. In the past few decades, modulation of anticancer drug resistance plays little role in benefit of clinical outcomes due to complex drug resistance mechanisms. Mitophagy, an important mitochondrial quality control system, selectively degrades excessive or damaged mitochondria by autophagy. Accumulating reports are suggesting that dysregulation of mitophagy contributes to neoplastic progression and drug resistance in various types of tumors. Mitophagy was originally thought to be an onco-suppressor that maintains cellular homeostasis and prevents oncogenic transformation. On the other hand, mitophagy promotes cancer cell survival under cytotoxic stress by degrading damaged mitochondria and reducing mitochondrial reactive oxygen species. Therefore, induction and inhibition of mitophagy in cancer drug resistance are controversial. In this review, we summarize current knowledge on the dual role of mitophagy in cancer drug resistance.