OMA1-mediated OPA1 processing in Phb2^NKO mice and mitochondrial ultrastructure. (A and B) L-OPA1 is stabilized upon deletion of Oma1 in Phb2^NKO mice. Hippocampal lysates isolated from 14-wk-old (A) or 18-wk-old (B) mice were analyzed by immunoblotting. SDHA was used as a loading control. (C) Hippocampal DG neurons of Phb2^NKOOma1^ko/ko mice contain large, swollen mitochondria lacking cristae. Analysis of mitochondrial ultrastructure in DG neurons of 6-, 14-, and 18-wk-old mice by transmission electron microscopy. Bar, 1.2 µm. (D) Impaired OPA1 oligomerization in Phb2^NKO and Phb2^NKOOma1^ko/ko mitochondria. OPA1 complex formation was analyzed in hippocampal mitochondria isolated from 18-wk-old mice of the indicated genotypes cross-linked with 1 mM EDC. OPA1 oligomers were visualized by immunoblotting (left panel), and complex levels were quantified using ImageJ (right panel; n = 4). HSPA9 was used as a loading control. O, oligomers; M, monomers. **, P ≤ 0.01; ***, P ≤ 0.001.