Hsp22 is the key sensor and balancer in mitochondrial dynamic associated metabolic reprogramming

Abstract

Altered mitochondrial dynamics are commonly seen in tumors and Parkinsons disease (PD), but the exact mechanism is unclear. We observed in tumor and PD flies, interference of mitochondrial fission or fusion reverses metabolic reprogramming and attenuates pathogenic phenotypes, indicating the rebalanced mitochondrial dynamics can re-establish cellular homeostasis. Surprisingly, we found Hsp22 is highly induced in tumor and PD flies. Hence, Hsp22 overexpression, not only suppressed RAS tumor flies, hepatocellular carcinoma mice, but also rescued PINK1B9 PD flies associating with restored mitochondrial homeostasis and reversing metabolic reprogramming. We speculate that mitochondrial dynamics is normally in a constant dynamic equilibrium, as if on a continually oscillating seesaw, tumor and PD are like the two extreme states of the seesaw which can be corrected by the promising target, Hsp22. One Sentence SummaryMitochondrial dynamics defects including tumor and PD lead to metabolic reprogramming accompanied with Hsp22 induction, vice versa, overexpression of Hsp22 reverses the mitochondrial dynamic dysfunction caused pathogenic metabolism.