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In situ architecture of Opa1-dependent mitochondrial cristae remodeling.

Michelle Y FryPaula P NavarroXingping QinZintis IndeVirly Y AnandaCamila Makhlouta LugoPusparanee HakimBridget E LuceYifan GeJulie L McDonaldIlzat AliLeillani L HaBenjamin P KleinstiverDavid C ChanKristopher SarosiekLuke H Chao
Published in: bioRxiv : the preprint server for biology (2023)
Cristae membrane state plays a central role in regulating mitochondrial function and cellular metabolism. The protein Optic atrophy 1 (Opa1) is an important crista remodeler that exists as two forms in the mitochondrion, a membrane-anchored long form (l-Opa1) and a processed short form (s-Opa1). The mechanisms for how Opa1 influences cristae shape have remained unclear due to the lack of native 3D views of cristae morphology. We perform in situ cryo-electron tomography of cryo-focused ion beam milled mouse embryonic fibroblasts to understand how each form of Opa1 influences cristae architecture. In our tomograms, we observe elongated mitochondria with a stacking phenotype, and an absence of tubular cristae, when only l-Opa1 is present. In contrast, when mitochondria contain mainly s-Opa1, we observe irregular cristae packing, an increase in globular cristae, and decreased matrix condensation. Notably, we find the absence of l-Opa1 results in mitochondria with wider cristae junctions. BH3 profiling reveals that absence of l-Opa1 reduces cytochrome c release in response to pro-apoptotic stimuli. We discuss the implications Opa1-dependent cristae morphologies in cell death initiation.
Keyphrases
  • cell death
  • high resolution
  • reactive oxygen species
  • mass spectrometry
  • endoplasmic reticulum
  • single cell
  • endothelial cells
  • amino acid
  • contrast enhanced