Completion of mitochondrial division requires the intermembrane space protein Mdi1/Atg44

Mitochondria are double membrane-bound organelles whose morphology and cellular distribution are controlled by the dynamic processes of fusion and fission. This study shows that mitochondrial fission, performed by the cytosolic dynamin-related protein Dnm1, requires the coordinated activity of a protein that localizes inside the organelle. Mitochondria are highly dynamic double membrane-bound organelles that maintain their shape in part through fission and fusion. Mitochondrial fission is performed by a dynamin-related protein, Dnm1 (Drp1 in humans), that constricts and divides the mitochondria in a GTP hydrolysis-dependent manner. However, it is unclear whether factors inside mitochondria help coordinate the process and if Dnm1/Drp1 activity is sufficient to complete the fission of both mitochondrial membranes. Here, we identify an intermembrane space protein required for mitochondrial fission in yeast, which we propose to name Mdi1 (also named Atg44). Loss of Mdi1 causes mitochondrial hyperfusion due to defects in fission, but not the lack of Dnm1 recruitment to mitochondria. Mdi1 is conserved in fungal species, and its homologs contain an amphipathic & alpha;-helix, mutations of which disrupt mitochondrial morphology. One model is that Mdi1 distorts mitochondrial membranes to enable Dnm1 to robustly complete fission. Our work reveals that Dnm1 cannot efficiently divide mitochondria without the coordinated function of Mdi1 inside mitochondria.

Automated summary

This study reveals the importance of a protein called Mdi1 in coordinating mitochondrial fission. Loss of Mdi1 leads to mitochondrial hyperfusion, suggesting its role in regulating fission. This work highlights the crucial role of Mdi1 in efficient mitochondrial division.