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      Pathways shaping the mitochondrial inner membrane

      review-article
      ,
      Open Biology
      The Royal Society
      ATP synthase, cristae, Mgm1, MICOS, mitochondrial lipids, Saccharomyces cerevisiae

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          Abstract

          Abstract

          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.

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          Most cited references219

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          Membrane lipids: where they are and how they behave.

          Throughout the biological world, a 30 A hydrophobic film typically delimits the environments that serve as the margin between life and death for individual cells. Biochemical and biophysical findings have provided a detailed model of the composition and structure of membranes, which includes levels of dynamic organization both across the lipid bilayer (lipid asymmetry) and in the lateral dimension (lipid domains) of membranes. How do cells apply anabolic and catabolic enzymes, translocases and transporters, plus the intrinsic physical phase behaviour of lipids and their interactions with membrane proteins, to create the unique compositions and multiple functionalities of their individual membranes?
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            An ER-mitochondria tethering complex revealed by a synthetic biology screen.

            Communication between organelles is an important feature of all eukaryotic cells. To uncover components involved in mitochondria/endoplasmic reticulum (ER) junctions, we screened for mutants that could be complemented by a synthetic protein designed to artificially tether the two organelles. We identified the Mmm1/Mdm10/Mdm12/Mdm34 complex as a molecular tether between ER and mitochondria. The tethering complex was composed of proteins resident of both ER and mitochondria. With the use of genome-wide mapping of genetic interactions, we showed that the components of the tethering complex were functionally connected to phospholipid biosynthesis and calcium-signaling genes. In mutant cells, phospholipid biosynthesis was impaired. The tethering complex localized to discrete foci, suggesting that discrete sites of close apposition between ER and mitochondria facilitate interorganelle calcium and phospholipid exchange.
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              Mitochondrial form and function.

              Mitochondria are one of the major ancient endomembrane systems in eukaryotic cells. Owing to their ability to produce ATP through respiration, they became a driving force in evolution. As an essential step in the process of eukaryotic evolution, the size of the mitochondrial chromosome was drastically reduced, and the behaviour of mitochondria within eukaryotic cells radically changed. Recent advances have revealed how the organelle's behaviour has evolved to allow the accurate transmission of its genome and to become responsive to the needs of the cell and its own dysfunction.
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                Author and article information

                Contributors
                Journal
                Open Biol
                Open Biol
                RSOB
                royopenbio
                Open Biology
                The Royal Society
                2046-2441
                December 1, 2021
                December 2021
                : 11
                : 12
                : 210238
                Affiliations
                Institut für Zellbiologie, Universität Bayreuth, , 95440 Bayreuth, Germany
                Author information
                http://orcid.org/0000-0003-0149-042X
                http://orcid.org/0000-0002-2991-1604
                Article
                rsob210238
                10.1098/rsob.210238
                8633786
                34847778
                7762510a-6f18-4118-ad9b-9ee117d94f97
                © 2021 The Authors.

                Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.

                History
                : August 13, 2021
                : November 4, 2021
                Funding
                Funded by: Elitenetzwerk Bayern, http://dx.doi.org/10.13039/501100008848;
                Award ID: Biological Physics
                Funded by: Deutsche Forschungsgemeinschaft, http://dx.doi.org/10.13039/501100001659;
                Award ID: 433461293
                Award ID: 459304237
                Categories
                1001
                33
                Review
                Review Articles

                Life sciences
                atp synthase,cristae,mgm1,micos,mitochondrial lipids,saccharomyces cerevisiae
                Life sciences
                atp synthase, cristae, mgm1, micos, mitochondrial lipids, saccharomyces cerevisiae

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