Effects of localpHon the formation and regulation of cristae morphologies

Abstract

Cristae, folded subcompartments of the inner mitochondrial membrane (IMM), have complex and dynamic morphologies. Since cristae are the major site of adenosine triphosphate synthesis, morphological changes of cristae have been studied in relation to functional states of mitochondria. In this sense, investigating the functional and structural significance of cristae may be critical for understanding progressive mitochondrial dysfunction. However, the detailed mechanisms of the formation and regulation of these cristae structures have not been fully elucidated. Among the hypotheses concerning the regulation of cristae morphologies, we exclusively investigate the effects of the local pH gradient on the cristae morphologies by using a numerical model. An area-difference induced curvature of the membrane is modeled as a function of local pH. This curvature is then applied to the finite element model of a closed lipid bilayer in order to find the energetically favorable membrane configuration. From this study, we substantiate the hypothesis that a tubular crista structure can be formed and regulated by the local pH gradient. Through the simulations with various initial conditions, we further demonstrate that the diameter of a crista is mainly determined by the local pH gradient, and the energetically favorable direction of crista growth is perpendicular to the longitudinal axis of a mitochondrion. Finally, the simulation results at the mitochondrial scale suggest that the cristae membrane may have a lower local pH value and/or a higher cardiolipin composition than the other parts of the IMM.

The chimeric origin of the cardiolipin biosynthetic pathway in the Eukarya domain

“…To support this view, recent evidence has demonstrated that liposomes containing the same composition of mitochondrial membranes are responsive to local pH gradients producing invaginations similar to those observed in the mitochondrial cristae. This phenomenon was specific for CL since other anionic phospholipids such as PS, PI or PG did not present this behavior [55][56][57]. Besides its non-bilayer properties (2), by chance, the most advantageous order was positively selected and represents the modern day eukaryote pathway present in Opistokontha.…”

Mitochondrial Cristae Architecture and Functions: Lessons from Minimal Model Systems

“…Intermonolayer friction also plays an important role in the relaxation dynamics of these deformations. An additional model simulating the morphologies of the IMM at the mitochondrial scale for given pH profiles was introduced by another group [ 92 ], confirming the possible role of CL in cristae formation, and suggesting that within cristae, a lower local pH value could exist [ 93 ], as well as a higher CL proportion than the other parts of the IMM.…”

Tracking intra‐ and inter‐organelle signaling of mitochondria

“…Since the OMM is generally permeable due to voltage‐dependent anion channel (VDAC) , the CJ seems to form a diffusion barrier for protons, creating an isolated space for the activity of F O F 1 ‐ATP synthase and respiratory chain complexes with lateral pH gradients . Computational models and in vitro experiments have shown that low pH causes cristae invaginations of the IMM based on the electrostatic induced negative curvature of the outer CM leaflet . Besides the direct involvement of the F O F 1 ‐ATP synthase in cristae formation and morphology , an indirect effect of CM localized respiratory supercomplexes mediated by the decreased pH in the CJ might be an important factor in cristae biogenesis and shape definition .…”