Reduction of the ATPase inhibitory factor 1 (IF(1)) leads to visual impairment in vertebrates

In vertebrates, mitochondria are tightly preserved energy producing organelles, which sustain nervous system development and function. The understanding of proteins that regulate their homoeostasis in complex animals is therefore critical and doing so via means of systemic analysis pivotal to inform pathophysiological conditions associated with mitochondrial deficiency. With the goal to decipher the role of the ATPase inhibitory factor 1 (IF(1)) in brain development, we employed the zebrafish as elected model reporting that the Atpif1a(−/−) zebrafish mutant, pinotage (pnt(tq209)), which lacks one of the two IF(1) paralogous, exhibits visual impairment alongside increased apoptotic bodies and neuroinflammation in both brain and retina. This associates with increased processing of the dynamin-like GTPase optic atrophy 1 (OPA1), whose ablation is a direct cause of inherited optic atrophy. Defects in vision associated with the processing of OPA1 are specular in Atpif1(−/−) mice thus confirming a regulatory axis, which interlinks IF(1) and OPA1 in the definition of mitochondrial fitness and specialised brain functions. This study unveils a functional relay between IF(1) and OPA1 in central nervous system besides representing an example of how the zebrafish model could be harnessed to infer the activity of mitochondrial proteins during development.