Implications of Therapy-Induced Selective Autophagy on Tumor Metabolism and Survival

Figure 1

Anticancer agents may activate selective forms of autophagy by causing ΔΨm depolarization, nuclear damage, and misfolded protein aggregates. (1) Drugs that open mPTPs are known to cause ΔΨm depolarization, which may result in the recruitment of PINK1 and Parkin. It is hypothesized that this would promote mitochondrial polyubiquitination and selective targeting to the autophagosome through the LC3:ubiquitin adapter proteins, such as p62. (2) DNA damaging agents may promote the selective autophagy of structurally damaged portions of nuclei in mammals in a process dependent on the cleavage of lamin and emerin intermediate filaments in the nuclear periplasm. To date, the mammalian adapter proteins that target the autophagosome to the nucleus have not been identified. (3) Drugs that inhibit the proteosome are known to cause an accumulation of misfolded protein aggregates in tumor cells, which results in Parkin mediated polyubiquitination and targeting to the autophagosome through p62.