Finding. A dilated-cardiomyopathy exome set yields a rare de novo OPA1 change, c.563C>T, p.Pro188Leu. Gupta, Mohapatra and colleagues cannot find it in 100 controls or in 1000 Genomes, IndiGenomes, or GenomeAsia 100k (GnomAD 0.000069). Structure says the protein is bent (RMSD 3.5 angstrom) and more open to the protease OMA1, which would chew OPA1 and fragment mitochondria. In H9C2 cardiomyoblasts that story holds: less OPA1 protein, shattered networks, weaker membrane potential, less ATP, less oxygen consumption, more cytosolic calcium and ROS, fewer mtDNA copies, more caspase-3/9 and a higher Bax/Bcl-2 ratio.
Why this paper matters OPA1 is usually an optic-atrophy and dominant-optic-atrophy-plus gene. A de novo DCM allele with a cardiomyoblast bioenergetic crash is how the same GTPase becomes a heart gene. The OMA1-access idea is a testable processing mechanism.
Score 88. Core fusion GTPase, heart, a full organelle panel. Confidence is medium: one patient, one cell line.
What to do with it If you sequence DCM, add OPA1. If you model Pro188Leu, blot long versus short OPA1 and cristae. Do not call it proven human cristae disease from H9C2 alone.