Cristae formation is a mechanical buckling event controlled by the inner mitochondrial membrane lipidome

• DOI: 10.15252/embj.2023114054
• Publication Date: 2023-11-07T10:31:04Z
• Authors: Kailash Venkatraman; Christopher T Lee; Guadalupe C Garcia; Arijit Mahapatra; Daniel Milshteyn; Guy Perkins; Keun‐Young Kim; H Amalia Pasolli; Sebastien Phan; Jennifer Lippinco...; Mark H Ellisman; Padmini Rangamani; Itay Budin
• Keywords: Membrane Curvature; Lipidome; Cardiolipins

Abstract Cristae are high‐curvature structures in the inner mitochondrial membrane (IMM) that crucial for ATP production. While cristae‐shaping proteins have been defined, analogous lipid‐based mechanisms yet to be elucidated. Here, we combine experimental lipidome dissection with multi‐scale modeling investigate how lipid interactions dictate IMM morphology and generation. When modulating phospholipid (PL) saturation engineered yeast strains, observed a surprisingly abrupt breakpoint topology driven by continuous loss of synthase organization at cristae ridges. We found cardiolipin (CL) specifically buffers against curvature loss, an effect is independent dimerization. To explain this interaction, developed continuum model tubule formation integrates both protein‐mediated curvatures. This highlighted snapthrough instability, which drives collapse upon small changes properties. also showed essential low‐oxygen conditions promote PL saturation. These results demonstrate mechanical function dependent on surrounding protein components IMM.