Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding

Zhang, Danyang; Zhang, Yan; Ma, Jun; Zhu, Chunmei; Niu, Tongxin; Chen, Wenbo; Pang, Xiaoyun; Zhai, Yujia; Sun, Fei

doi:10.7554/elife.50294

Cited by 39 publications

(50 citation statements)

References 51 publications

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“…Parallel investigations of the cryo-EM structure of liposomes coated with human S-OPA1, as well as X-ray crystallography of the yeast S-Mgm1 support the findings made about fungal Mgm1 protein regarding the importance of its oligomerization, GTPase function activation, domain structure, and its membrane curvature induction activity (Zhang et al 2020). Sequence analysis of the human S-OPA1 as well as yeast S-Mgm1 suggest that their C-terminal domains (corresponding to the paddle domain of Chaetomium Mgm1) exert membrane binding and deformation via an AH.…”

Section: Mgm1/opa1-cristae Membranessupporting

confidence: 60%

“…Liposome co-sedimentation assays with recombinantly purified short isoform of OPA1 revealed a strong binding preference to the negatively charged liposomes containing, for example, phosphatidylserine (PS) or cardiolipin (CL) (Ban et al 2010). Membrane binding promoted the rather low basal GTPase activity of OPA1 up to 100 folds, as well as assembly of OPA1 into higher order oligomers, as detected by homo-bifunctional cross-linking experiments (Ban et al 2010;Zhang et al 2020). Fluorescence microscopy, negative stain transmission EM, as well as electron cryo-microscopy showed that these higher order oligomers assemble into a regular pattern and induce protrusion of lipid tubules from the cardiolipin-containing liposomes (Frezza et al 2006;Ban et al 2010;Zhang et al 2020).…”

Section: Mgm1/opa1-cristae Membranesmentioning

confidence: 96%

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Protein-dependent membrane remodeling in mitochondrial morphology and clathrin-mediated endocytosis

Tarasenko

Meinecke

2021

Eur Biophys J

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Cellular membranes can adopt a plethora of complex and beautiful shapes, most of which are believed to have evolved for a particular physiological reason. The closely entangled relationship between membrane morphology and cellular physiology is strikingly seen in membrane trafficking pathways. During clathrin-mediated endocytosis, for example, over the course of a minute, a patch of the more or less flat plasma membrane is remodeled into a highly curved clathrin-coated vesicle. Such vesicles are internalized by the cell to degrade or recycle plasma membrane receptors or to take up extracellular ligands. Other, steadier, membrane morphologies can be observed in organellar membranes like the endoplasmic reticulum or mitochondria. In the case of mitochondria, which are double membrane-bound, ubiquitous organelles of eukaryotic cells, especially the mitochondrial inner membrane displays an intricated ultrastructure. It is highly folded and consequently has a much larger surface than the mitochondrial outer membrane. It can adopt different shapes in response to cellular demands and changes of the inner membrane morphology often accompany severe diseases, including neurodegenerative- and metabolic diseases and cancer. In recent years, progress was made in the identification of molecules that are important for the aforementioned membrane remodeling events. In this review, we will sum up recent results and discuss the main players of membrane remodeling processes that lead to the mitochondrial inner membrane ultrastructure and in clathrin-mediated endocytosis. We will compare differences and similarities between the molecular mechanisms that peripheral and integral membrane proteins use to deform membranes.

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Section: Mgm1/opa1-cristae Membranessupporting

confidence: 60%

Section: Mgm1/opa1-cristae Membranesmentioning

confidence: 96%

Protein-dependent membrane remodeling in mitochondrial morphology and clathrin-mediated endocytosis

Tarasenko

Meinecke

2021

Eur Biophys J

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“…This may indicate that Opa1 processing is not necessary for fusion, and that overexpression of short OPA1 forms trigger mitochondrial fragmentation in Yme1l −/− cells (61). However, recent studies show that S-OPA1 play a role in MIM fusion, and cryo-electron microscopy (cryo-EM) studies reveal that S-OPA1 has a dynamin-like structure and employs dynamin-like power stroke membrane remodeling for MIM fusion (62). Moreover, moderate levels of S-OPA1 together with L-OPA1 are required for efficient and fast membrane pore opening during the fusion process, but excess levels of S-OPA1 inhibit fusion activity (63).…”

Section: The Mammalian Mitochondrial Fusion Machinerymentioning

confidence: 99%

Regulation of Mammalian Mitochondrial Dynamics: Opportunities and Challenges

et al. 2020

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Mitochondria are highly dynamic organelles and important for a variety of cellular functions. They constantly undergo fission and fusion events, referred to as mitochondrial dynamics, which affects the shape, size, and number of mitochondria in the cell, as well as mitochondrial subcellular transport, mitochondrial quality control (mitophagy), and programmed cell death (apoptosis). Dysfunctional mitochondrial dynamics is associated with various human diseases. Mitochondrial dynamics is mediated by a set of mitochondria-shaping proteins in both yeast and mammals. In this review, we describe recent insights into the potential molecular mechanisms underlying mitochondrial fusion and fission, particularly highlighting the coordinating roles of different mitochondria-shaping proteins in the processes, as well as the roles of the endoplasmic reticulum (ER), the actin cytoskeleton and membrane phospholipids in the regulation of mitochondrial dynamics. We particularly focus on emerging roles for the mammalian mitochondrial proteins Fis1, Mff, and MIEFs (MIEF1 and MIEF2) in regulating the recruitment of the cytosolic Drp1 to the surface of mitochondria and how these proteins, especially Fis1, mediate crosstalk between the mitochondrial fission and fusion machineries. In summary, this review provides novel insights into the molecular mechanisms of mammalian mitochondrial dynamics and the involvement of these mechanisms in apoptosis and autophagy.

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“…The unique ability of S-Mgm1 to form a helical lattice on the outside and inside of lipid tubes, in combination with flexibility to form either left-or right-handed helices, could explain the multifaceted activity of S-Mgm1 in coordinating fusion and fission of IM in addition to controlling cristae width. Cryo-ET revealed that addition of S-OPA1 to liposomes tubulated them via the formation of helical lattices independently of S-OPA1 GTPase activity [50]. Moreover, studies in baker's yeast have led to the Oxidative phosphorylation (OXPHOS): the process in which NADH/FADH 2 are oxidized to generate the proton motive force used for formation of ATP employing respiratory chain complexes I to IV as well as complex V, the F 1 F o ATP synthase.…”

Section: Opa1 As the Regulator Of Cristae Remodeling: New Roles For Amentioning

confidence: 99%

Cristae Membrane Dynamics – A Paradigm Change

Kondadi

Anand

Reichert

2020

Trends in Cell Biology

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Mitochondria are dynamic organelles that have essential metabolic and regulatory functions. Earlier studies using electron microscopy (EM) revealed an immense diversity in the architecture of cristaeinfoldings of the mitochondrial inner membrane (IM)in different cells, tissues, bioenergetic and metabolic conditions, and during apoptosis. However, cristae were considered to be largely static entities. Recently, advanced super-resolution techniques have revealed that cristae are independent bioenergetic units that are highly dynamic and remodel on a timescale of seconds. These advances, coupled with mechanistic and structural studies on key molecular players, such as the MICOS (mitochondrial contact site and cristae organizing system) complex and the dynamin-like GTPase OPA1, have changed our view on mitochondria in a fundamental way. We summarize these recent findings and discuss their functional implications. The Changing Paradigm of Mitochondrial IM Structure and Dynamics Mitochondria are double-membrane-enclosed organelles of endosymbiotic origin that harbor an outer membrane (OM) and an inner membrane (IM). The immense diversity of mitochondrial ultrastructures was elucidated by electron microscopy (EM) over recent decades, and various models of cristae organization have been put forward [1]. The use of 3D electron tomography (ET) in the 1990s to decipher cristae structure by Terry Frey and Carmen Mannella led to seminal contributions that mark a shift in our view on cristae organization [2-4]. Cristae were no longer seen as extended, broad infoldings of the IM but instead were connected to the inner boundary membrane (IBM; see Glossary) by pore-or slit-like structures called crista junctions (CJs) (Box 1). CJs were proposed to act as diffusion barriers for membrane and soluble proteins, metabolites, and even protons [4,5]. Later studies confirmed that the IM is indeed subcompartmentalized [6-8]. Despite these advances and the conception that cristae are variable in structure, cristae were considered to be static under a particular physiological condition. This view was certainly biased because mitochondrial ultrastructure was studied using EM at high spatial resolution, although in fixed sample specimens. The static nature of cristae was propagated in textbooks for the past 60 years. In the 1960s, Charles Hackenbrock observed that addition of ADP could reversibly change the IM connectivity coupled with changes in mitochondrial matrix volume in isolated rat liver mitochondria [9,10], and this was corroborated using 3D ET experiments almost three decades later [3,5,11]. The latter studies also led to the proposal that cristae membrane (CM) reorganization might involve membrane fusion and fission events [5]. In addition, induction of apoptosis was accompanied by changes in the IM shape, connectivity, and matrix volume [12], which strongly suggested that cristae can dynamically change their structure. Hence, there were clear indications that CM remodeling can be induced by altered physiological conditions. The us...

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Cryo-EM structures of S-OPA1 reveal its interactions with membrane and changes upon nucleotide binding

Cited by 39 publications

References 51 publications

Protein-dependent membrane remodeling in mitochondrial morphology and clathrin-mediated endocytosis

Protein-dependent membrane remodeling in mitochondrial morphology and clathrin-mediated endocytosis

Regulation of Mammalian Mitochondrial Dynamics: Opportunities and Challenges

Cristae Membrane Dynamics – A Paradigm Change

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