Research Paper Volume 7, Issue 9 pp 701—712

Figure 5. Mitochondrial hyperfusion and UPR^mt 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 UPR^mt. (B) While mitochondrial hyperfusion helps to maintain ATP level in response to a reduction in complex IV activity [11], UPR^mt 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].