The Bacterial ZapA-like Protein ZED Is Required for Mitochondrial Division

Summary Bacterial cell division systems that include FtsZ are found throughout prokaryotes [1]. Mitochondria arose from an endosymbiotic α-proteobacterial ancestor and proliferate by division [2–4]. However, how the mitochondrial division system was established from bacterial division is not clear. Here, we have isolated intact mitochondrial division (MD) machineries from the primitive red alga Cyanidioschyzon merolae and identified a bacterial ZapA-like protein, ZED, that constricts the basal structure of MD machinery with FtsZ. ZED contains a predicted mitochondrial transit signal and two coiled-coil regions and has partial homology with the bacterial division protein ZapA [5]. Cytological studies revealed that ZED accumulates to form a ring structure that colocalizes with FtsZ beneath the inner membrane. ZED proteins are expressed just before mitochondrial division. The short-form ZED (S-ZED) then appears at the mitochondrial constriction phase. Protein-protein interaction analysis and transient expression of antisense against ZED showed that S-ZED interacts with FtsZ1 to constitute the basal structure of the MD machinery and is required for mitochondrial division. We also demonstrate compelling functional similarity between bacterial ZapA and mitochondrial ZED, suggesting that the bacterial cell division system was incorporated into the MD machinery with remodeling of bacterial division proteins during evolution.