Cardiolipin and mitochondrial cristae organization

Abstract

A fundamental question in cell biology, under investigation for over six decades, is the structural organization of mitochondrial cristae. Long known to harbor electron transport chain proteins, crista membrane integrity is key to establishment of the proton gradient that drives oxidative phosphorylation. Visualization of cristae morphology by electron microscopy / tomography has provided evidence that cristae are tube-like extensions of the mitochondrial inner membrane (IM) that project into the matrix space. Reconciling ultrastructural data with the lipid composition of the IM provides support for a continuously curved cylindrical bilayer capped by a dome-shaped tip. Strain imposed by the degree of curvature is relieved by an asymmetric distribution of phospholipids in monolayer leaflets that comprise cristae membranes. The signature mitochondrial lipid, cardiolipin (∼18 % of IM phospholipid mass), and phosphatidylethanolamine (34 %) segregate to the negatively curved monolayer leaflet facing the crista lumen while the opposing, positively curved, matrix-facing monolayer leaflet contains predominantly phosphatidylcholine. Associated with cristae are numerous proteins that function in distinctive ways to establish and/or maintain their lipid repertoire and structural integrity. By combining unique lipid components with a set of protein modulators, crista membranes adopt and maintain their characteristic morphological and functional properties. Once established, cristae ultrastructure has a direct impact on oxidative phosphorylation, apoptosis, fusion / fission as well as diseases of compromised energy metabolism.

Omnipresent Maxwell's demons orchestrate information management in living cells

“…For example, ClsA colocalizes with its cardiolipin products (Romantsov et al, 2018). In the same way, cardiolipins are closely associated with cristae in mitochondria (Ikon and Ryan, 2017;Schlame and Greenberg, 2017;Oemer et al, 2018). These molecules can act as seeds to induce local curvature in an autocatalytic way.…”

Assembly and Characterization of Biocompatible Coenzyme Q10‐Enriched Lipid Nanoparticles

“…The IMM is unique in that it is comprised of ~75% protein and ~25% lipid, making it one the most protein‐rich membranes in nature. Another important feature of the IMM is that it is a highly curved membrane, containing phospholipids that impose negative membrane curvature pressure on bilayers (Ikon and Ryan, 2017). It is currently unknown precisely how CoQ 10 is accommodated in membranes, whether it is unusually long, 50‐carbon isoprene tail is fully extended, folds back on itself or both.…”

Alteration of cardiolipin-dependent mitochondrial coupling in muscle protects against obesity

“…Importance of mitochondrial membranes lipid composition per se in the functional structure of cristae is exemplified in HACD1-deficient muscles by unaltered levels of all the presently known proteins acting in cristae shaping and function, such as the ATP synthase, respiratory supercomplexes and the Micos complex. CL is known to play an essential role in cristae biogenesis (Ikon and Ryan, 2017b;Khalifat et al, 2008) and through cristae remodeling, may also trigger the dynamic adaptation of mitochondria, with reversible modifications in cristae structure observed to meet variable metabolic needs of the cell. Indeed low ADP conditions prompt cristae to organize into a so called orthodox structure, whilst upon high ADP availability, they rather organize into a condensed structure, characterized by a small amount of matrix and abundant cristae (Hackenbrock, 1966) that support optimal ATP production (Lizana et al, 2008;Mannella, 2006;Song et al, 2013).…”