scholarly journals Pathways shaping the mitochondrial inner membrane

Open Biology ◽  
2021 ◽  
Vol 11 (12) ◽  
Author(s):  
Till Klecker ◽  
Benedikt Westermann
Keyword(s):  
Atp Synthase ◽  
Lipid Composition ◽  
Mitochondrial Membrane ◽  
Contact Site ◽  
Dimer Formation ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Mitochondrial Atp Synthase ◽  
Evolutionarily Conserved ◽  
Mitochondrial Lipid

Mitochondria are complex organelles with two membranes. Their architecture is determined by characteristic folds of the inner membrane, termed cristae. Recent studies in yeast and other organisms led to the identification of four major pathways that cooperate to shape cristae membranes. These include dimer formation of the mitochondrial ATP synthase, assembly of the mitochondrial contact site and cristae organizing system (MICOS), inner membrane remodelling by a dynamin-related GTPase (Mgm1/OPA1), and modulation of the mitochondrial lipid composition. In this review, we describe the function of the evolutionarily conserved machineries involved in mitochondrial cristae biogenesis with a focus on yeast and present current models to explain how their coordinated activities establish mitochondrial membrane architecture.

scholarly journals Mitochondrial Membrane Dynamics—Functional Positioning of OPA1

Antioxidants ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 186 ◽  
Author(s):  
Hakjoo Lee ◽  
Yisang Yoon
Keyword(s):  
Mitochondrial Membrane ◽  
Proteolytic Cleavage ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Functional Differences ◽  
New Information ◽  
New Development

The maintenance of mitochondrial energetics requires the proper regulation of mitochondrial morphology, and vice versa. Mitochondrial dynamins control mitochondrial morphology by mediating fission and fusion. One of them, optic atrophy 1 (OPA1), is the mitochondrial inner membrane remodeling protein. OPA1 has a dual role in maintaining mitochondrial morphology and energetics through mediating inner membrane fusion and maintaining the cristae structure. OPA1 is expressed in multiple variant forms through alternative splicing and post-translational proteolytic cleavage, but the functional differences between these variants have not been completely understood. Recent studies generated new information regarding the role of OPA1 cleavage. In this review, we will first provide a brief overview of mitochondrial membrane dynamics by describing fission and fusion that are mediated by mitochondrial dynamins. The second part describes OPA1-mediated fusion and energetic maintenance, the role of OPA1 cleavage, and a new development in OPA1 function, in which we will provide new insight for what OPA1 does and what proteolytic cleavage of OPA1 is for.

scholarly journals Mitochondrial lipid transport and biosynthesis: A complex balance

2016 ◽  
Vol 214 (1) ◽  
pp. 9-11 ◽  
Author(s):  
Bruno Mesmin
Keyword(s):  
Metabolic Enzymes ◽  
Lipid Transport ◽  
Contact Site ◽  
Inner Membrane ◽  
Cell Biol ◽  
Mitochondrial Lipid ◽  
Mitochondrial Complexes ◽  
Mitochondrial Lipids

Little is known about how mitochondrial lipids reach inner membrane–localized metabolic enzymes for phosphatidylethanolamine synthesis. Aaltonen et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201602007) and Miyata et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201601082) now report roles for two mitochondrial complexes, Ups2–Mdm35 and mitochondrial contact site and cristae organizing system, in the biosynthesis and transport of mitochondrial lipids.

scholarly journals MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Jonathan R Friedman ◽  
Arnaud Mourier ◽  
Justin Yamada ◽  
J Michael McCaffery ◽  
Jodi Nunnari
Keyword(s):  
Inner Membrane ◽  
Functional Roles ◽  
Respiratory Complexes ◽  
Growth Defects ◽  
Mitochondrial Inner Membrane ◽  
Complex Functions ◽  
Primary Determinant ◽  
Mitochondrial Defects ◽  
Mitochondrial Lipid ◽  
Redundant Functions

The conserved MICOS complex functions as a primary determinant of mitochondrial inner membrane structure. We address the organization and functional roles of MICOS and identify two independent MICOS subcomplexes: Mic27/Mic10/Mic12, whose assembly is dependent on respiratory complexes and the mitochondrial lipid cardiolipin, and Mic60/Mic19, which assembles independent of these factors. Our data suggest that MICOS subcomplexes independently localize to cristae junctions and are connected via Mic19, which functions to regulate subcomplex distribution, and thus, potentially also cristae junction copy number. MICOS subunits have non-redundant functions as the absence of both MICOS subcomplexes results in more severe morphological and respiratory growth defects than deletion of single MICOS subunits or subcomplexes. Mitochondrial defects resulting from MICOS loss are caused by misdistribution of respiratory complexes in the inner membrane. Together, our data are consistent with a model where MICOS, mitochondrial lipids and respiratory complexes coordinately build a functional and correctly shaped mitochondrial inner membrane.

scholarly journals Functional Analysis of Subunit e of the F1Fo-ATP Synthase of the Yeast Saccharomyces cerevisiae: Importance of the N-Terminal Membrane Anchor Region

2005 ◽  
Vol 4 (2) ◽  
pp. 346-355 ◽  
Author(s):  
Valerie Everard-Gigot ◽  
Cory D. Dunn ◽  
Brigid M. Dolan ◽  
Susanne Brunner ◽  
Robert E. Jensen ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Atp Synthase ◽  
Mitochondrial Membrane ◽  
Critical Role ◽  
Coiled Coil ◽  
Mitochondrial Morphology ◽  
Hydrophobic Region ◽  
Inner Membrane ◽  
E Protein ◽  
Subunit E

ABSTRACT Mitochondrial F1Fo-ATP synthase complexes do not exist as physically independent entities but rather form dimeric and possibly oligomeric complexes in the inner mitochondrial membrane. Stable dimerization of two F1Fo-monomeric complexes involves the physical association of two membrane-embedded Fo-sectors. Previously, formation of the ATP synthase dimeric-oligomeric network was demonstrated to play a critical role in modulating the morphology of the mitochondrial inner membrane. In Saccharomyces cerevisiae, subunit e (Su e) of the Fo-sector plays a central role in supporting ATP synthase dimerization. The Su e protein is anchored to the inner membrane via a hydrophobic region located at its N-terminal end. The hydrophilic C-terminal region of Su e resides in the intermembrane space and contains a conserved coiled-coil motif. In the present study, we focused on characterizing the importance of these regions for the function of Su e. We created a number of C-terminal-truncated derivatives of the Su e protein and expressed them in the Su e null yeast mutant. Mitochondria were isolated from the resulting transformant strains, and a number of functions of Su e were analyzed. Our results indicate that the N-terminal hydrophobic region plays important roles in the Su e-dependent processes of mitochondrial DNA maintenance, modulation of mitochondrial morphology, and stabilization of the dimer-specific Fo subunits, subunits g and k. Furthermore, we show that the C-terminal coiled-coil region of Su e functions to stabilize the dimeric form of detergent-solubilized ATP synthase complexes. Finally, we propose a model to explain how Su e supports the assembly of the ATP synthase dimers-oligomers in the mitochondrial membrane.

scholarly journals Uniform nomenclature for the mitochondrial contact site and cristae organizing system

2014 ◽  
Vol 204 (7) ◽  
pp. 1083-1086 ◽  
Author(s):  
Nikolaus Pfanner ◽  
Martin van der Laan ◽  
Paolo Amati ◽  
Roderick A. Capaldi ◽  
Amy A. Caudy ◽  
...  
Keyword(s):  
Large Protein ◽  
Contact Site ◽  
Inner Membrane ◽  
Future Studies ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Mitochondrial Inner Membrane ◽  
Large Protein Complex ◽  
Membrane Contact ◽  
Uniform Nomenclature

The mitochondrial inner membrane contains a large protein complex that functions in inner membrane organization and formation of membrane contact sites. The complex was variably named the mitochondrial contact site complex, mitochondrial inner membrane organizing system, mitochondrial organizing structure, or Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify the nomenclature and term the complex “mitochondrial contact site and cristae organizing system” and its subunits Mic10 to Mic60.

scholarly journals IF1, a natural inhibitor of mitochondrial ATP synthase, is not essential for the normal growth and breeding of mice

2013 ◽  
Vol 33 (5) ◽  
Author(s):  
Junji Nakamura ◽  
Makoto Fujikawa ◽  
Masasuke Yoshida
Keyword(s):  
Atp Synthase ◽  
Mouse Strain ◽  
Reactive Oxygen Species Generation ◽  
Atp Synthesis ◽  
Normal Growth ◽  
Test Results ◽  
Mitochondrial Atp Synthase ◽  
Evolutionarily Conserved ◽  
Natural Inhibitor ◽  
Synthesis Activity

IF1 is an endogenous inhibitor protein of mitochondrial ATP synthase. It is evolutionarily conserved throughout all eukaryotes and it has been proposed to play crucial roles in prevention of the wasteful reverse reaction of ATP synthase, in the metabolic shift from oxidative phosphorylation to glycolysis, in the suppression of ROS (reactive oxygen species) generation, in mitochondria morphology and in haem biosynthesis in mitochondria, which leads to anaemia. Here, we report the phenotype of a mouse strain in which IF1 gene was destroyed. Unexpectedly, individuals of this IF1-KO (knockout) mouse strain grew and bred without defect. The general behaviours, blood test results and responses to starvation of the IF1-KO mice were apparently normal. There were no abnormalities in the tissue anatomy or the autophagy. Mitochondria of the IF1-KO mice were normal in morphology, in the content of ATP synthase molecules and in ATP synthesis activity. Thus, IF1 is not an essential protein for mice despite its ubiquitous presence in eukaryotes.

scholarly journals Tim29 is a novel subunit of the human TIM22 translocase and is involved in complex assembly and stability

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Yilin Kang ◽  
Michael James Baker ◽  
Michael Liem ◽  
Jade Louber ◽  
Matthew McKenzie ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Intermembrane Space ◽  
Outer Mitochondrial Membrane ◽  
Carrier Proteins ◽  
Mitochondrial Import ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
C Terminus ◽  
The Stability ◽  
Human Complex

The TIM22 complex mediates the import of hydrophobic carrier proteins into the mitochondrial inner membrane. While the TIM22 machinery has been well characterised in yeast, the human complex remains poorly characterised. Here, we identify Tim29 (C19orf52) as a novel, metazoan-specific subunit of the human TIM22 complex. The protein is integrated into the mitochondrial inner membrane with it’s C-terminus exposed to the intermembrane space. Tim29 is required for the stability of the TIM22 complex and functions in the assembly of hTim22. Furthermore, Tim29 contacts the Translocase of the Outer Mitochondrial Membrane, TOM complex, enabling a mechanism for transport of hydrophobic carrier substrates across the aqueous intermembrane space. Identification of Tim29 highlights the significance of analysing mitochondrial import systems across phylogenetic boundaries, which can reveal novel components and mechanisms in higher organisms.

scholarly journals Stimulation of Mitochondrial ATP Synthase Activity – a New Diazoxide-Mediated Mechanism of Cardioprotection

2016 ◽  
pp. S119-S127 ◽  
Author(s):  
M. JAŠOVÁ ◽  
I. KANCIROVÁ ◽  
M. MURÁRIKOVÁ ◽  
V. FARKAŠOVÁ ◽  
I. WACZULÍKOVÁ ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Atp Synthase ◽  
Mitochondrial Membrane ◽  
Isolated Heart ◽  
Myocardial Infarct ◽  
Direct Interaction ◽  
Myocardial Infarct Size ◽  
Mitochondrial Atp Synthase ◽  
Mitochondrial Membrane Fluidity

Pharmacological preconditioning by diazoxide and a model of experimental streptozotocin-induced acute diabetes mellitus (STZ-DM) provided similar levels of cardioprotection assessed as limiting myocardial infarct size. The aim was to explore the possibility of existence of another in vitro mechanism, which could be contributory to cardioprotection mediated by diazoxide treatment. Mitochondrial membrane fluidity and ATP synthase activity in isolated heart mitochondria were determined under the influence of two factors, STZ-DM condition and treatment with diazoxide. Both factors independently increased the ATP synthase activity (p<0.05), as no interaction effect was observed upon the combination of STZ-DM with diazoxide. On the other hand, the mitochondrial membrane fluidity was significantly increased by STZ-DM only; no significant main effect for diazoxide was found. Based on the results from measurements of enzyme kinetics, we assume a direct interaction of diazoxide with the molecule of ATP synthase stimulated its activity by noncompetitive activation. Our present work revealed, for the first time, that cardioprotection induced by diazoxide may not be caused exclusively by mitochondrial KATP opening, but presumably also by a direct interaction of diazoxide with ATP synthase, although the mechanisms for achieving this activation cannot be fully delineated.

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