Mitochondrial Membrane Remodeling

Abstract

Mitochondria are key regulators of many important cellular processes and their dysfunction has been implicated in a large number of human disorders. Importantly, mitochondrial function is tightly linked to their ultrastructure, which possesses an intricate membrane architecture defining specific submitochondrial compartments. In particular, the mitochondrial inner membrane is highly folded into membrane invaginations that are essential for oxidative phosphorylation. Furthermore, mitochondrial membranes are highly dynamic and undergo constant membrane remodeling during mitochondrial fusion and fission. It has remained enigmatic how these membrane curvatures are generated and maintained, and specific factors involved in these processes are largely unknown. This review focuses on the current understanding of the molecular mechanism of mitochondrial membrane architectural organization and factors critical for mitochondrial morphogenesis, as well as their functional link to human diseases.

Mitochondrial Lipids: From Membrane Organization to Apoptotic Facilitation

“…Compartmentalization serves a function as specific bioenergetic processes are performed within the matrix, for instance the tricarboxylic acid cycle (TCA) or the beta-oxidation of fatty acids (FAs). Within the matrix also lie mitochondrial DNA and ribosomes where transcription and translation of the few mitochondrially encoded proteins occur [ 6 , 13 ].…”

“…The IMS has a much more complex and, as of today, much more elusive role. Protein sorting, redox balancing with glutathione oxidation and reduction, and most importantly, cytC release and apoptotic cascade activation, are some of the many functions regulated by the extremely confined, only 5% of mitochondrial space, IMS [ 6 , 13 , 14 ]. IMS itself is physically and functionally subdivided into at least two different compartments, the peripheral intermembrane space and the intracristae space (ICS) [ 15 ].…”

“…IMS itself is physically and functionally subdivided into at least two different compartments, the peripheral intermembrane space and the intracristae space (ICS) [ 15 ]. The peripheral IMS is a relatively reduced environment with high reduced glutathione (GSH) concentration, where protein and solute trafficking from the cytoplasm to the matrix and vice versa can safely take place [ 6 , 16 ]. Contrarily, ICS is much more oxidized and thus hostile, with yet a crucial function in mitochondrial respiration.…”

“…The two spaces and the associated IMM are dynamically yet strictly separated through a complex proteinic system anchored either directly or indirectly to the lipids of the IMM ( Figure 1 ) [ 17 ]. Protein–lipid and protein–protein interactions ensure that the ICS remains isolated from the rest of the IMS [ 6 ]. Disruption of the protein–lipid interactions interferes with the docking of several complexes to the IMM and often occurs during mitochondrial stress that leads to apoptosis.…”

“…Mitochondrial double membrane is the most intriguing feature of the organelle that shall inevitably be disturbed to allow cytC release; it differs from any other cellular membrane both in structure and subsequently in function as well. Moreover, mitochondrial membrane composition changes actively during the apoptotic process and facilitates initiation as well as completion of the phenomenon [ 4 , 6 ].…”