Principle of mitochondrial quality control with focus on OPA1 function and its contribution to mitochondrial network dynamics. DRP1 recruitment to mitochondria is necessary and sufficient for mitochondrial fission. In healthy mitochondria there is a continuous equilibrium between mitochondrial fission (top) and fusion (left side). Dysfunctional mitochondria can be repaired and rescued by re-fusion to the mitochondrial network (not depicted for the sake of clarity). OPA1L and OPA1S (together with MFN1/2 on the mitochondrial outer membrane) are necessary and sufficient for maintaining fusion competent mitochondria. Fusion is prevented in dysfunctional mitochondria by proteolytic cleavage of OPA1L to OPA1S (right side). The best-characterized example of dysfunctional mitochondria so far is dissipation of the mitochondrial membrane potential (ΔΨm), which leads to proteolytic cleavage of OPA1L by OMA1. OPA1 cleavage, however, occurs under various conditions enabling the integration of various parameters into mitochondrial network dynamics. Higd-1a, for example, regulates mitochondrial network dynamics by binding to OPA1L and thereby inhibiting its proteolytic cleavage. Dissipation of the mitochondrial membrane potential activates in the long run also the PINK1/parkin pathway (pink flag), which targets dysfunctional mitochondria for mitochondrial autophagy. OPA1L counteracts cytochrome C release and cell death (black flag) and therefore acts anti-apoptotic. OPA1S (presumably together with BNIP3) is necessary to promote cytochrome C release and cell death. This outer membrane permeabilization might be independent or happen in cooperation with BAX and DRP1 dependent outer membrane permeabilization (dotted line). BNIP3 is also necessary for mitochondrial autophagy and therefore could play an important role in the decision whether to remove single dysfunctional mitochondria or to recycle the whole cell by undergoing cell death.