Cristae formation is a mechanical buckling event controlled by the inner mitochondrial membrane lipidome
Abstract
Cristae are high‐curvature structures in the inner mitochondrial membrane (IMM) that are crucial for ATP production. While cristae‐shaping proteins have been defined, analogous lipid‐based mechanisms have yet to be elucidated. Here, we combine experimental lipidome dissection with multi‐scale modeling to investigate how lipid interactions dictate IMM morphology and ATP generation. When modulating phospholipid (PL) saturation in engineered yeast strains, we observed a surprisingly abrupt breakpoint in IMM topology driven by a continuous loss of ATP synthase organization at cristae ridges. We found that cardiolipin (CL) specifically buffers the inner mitochondrial membrane against curvature loss, an effect that is independent of ATP synthase dimerization. To explain this interaction, we developed a continuum model for cristae tubule formation that integrates both lipid and protein‐mediated curvatures. This model highlighted a snapthrough instability, which drives IMM collapse upon small changes in membrane properties. We also showed that cardiolipin is essential in low‐oxygen conditions that promote PL saturation. These results demonstrate that the mechanical function of cardiolipin is dependent on the surrounding lipid and protein components of the IMM.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 07, 2023
- Source ID
- 10.15252/embj.2023114054
Entities
People
- Arijit Mahapatra
- Christopher T Lee
- Daniel Milshteyn
- Guadalupe C Garcia
- Guy Perkins
- Hilda Amalia Pasolli
- Itay Budin
- Jennifer Lippincott‐schwartz
- Kailash Venkatraman
- Keun‐young Kim
- Mark H Ellisman
- Padmini Rangamani
- Sébastien Phan
Organizations
- Gordon and Betty Moore Foundation
- Howard Hughes Medical Institute
- National Institutes of Health
- National Science Foundation
- Office of Naval Research
- Salk Institute for Biological Studies
- United States Department of Energy
- University of California, San Diego