Research Paper Volume 7, Issue 9 pp 701—712

The loss of LRPPRC function induces the mitochondrial unfolded protein response


Figure 5. Mitochondrial hyperfusion and UPRmt act together to protect mitochondrial function. (A) Complex IV of the ETC is composed of mitochondria-encoded and nuclear-encoded subunits. Upon LRPPRC mma-1 RNAi, the level of mitochondria-encoded subunits decreases, leading to a reduction in complex IV activity, which triggers the mitochondrial hyperfusion response and an accumulation of unassembled nuclear-encoded subunits, which triggers UPRmt. (B) While mitochondrial hyperfusion helps to maintain ATP level in response to a reduction in complex IV activity [11], UPRmt helps to restore the balance between mitochondria-encoded and nuclear-encoded subunits of this complex. Mitochondrial hyperfusion can only compensate for reduced complex IV activity for a limited time. Prolonged inactivation of LRPPRC mma-1 eventually leads to mitochondrial fragmentation and drop in ATP level as previously shown [11].