scholarly journals Cryo-EM structures reveal a conformational change of SOPA1 during mitochondrial inner membrane fusion

2019 ◽  
Author(s):  
Danyang Zhang ◽  
Yan Zhang ◽  
Jun Ma ◽  
Tongxin Niu ◽  
Wenbo Chen ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Bound States ◽  
General Structure ◽  
Proteolytic Processing ◽  
Gtpase Domain ◽  
Inner Membrane ◽  
Unique Role ◽  
Mitochondrial Inner Membrane ◽  
Membrane Tubulation

ABSTRACTMammalian mitochondrial inner membrane fusion is mediated by OPA1(optic atrophy 1). Under physiological condition, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (LOPA1) and a soluble short isoform (SOPA1). A combination of LOPA1 and SOPA1 are required for membrane fusion, however, the relevant mechanism is not well understood. In this study, we investigate the cryo-EM structures of SOPA1 coated liposome tube at nucleotide-free and GTPγS bound states. SOPA1 exhibits a general structure of dynamin family and can assemble onto membrane in a helical array with a building block of dimer and thus induce membrane tubulation. A predicted amphipathic helix is discovered to mediate the tubulation activity of SOPA1. The binding of GTPγS causes a conformational rotation between GTPase domain and stalk region, and then induces a rearrangement of the helical array and an expansion of the tube, which is opposite to the behavior of other dynamin proteins, suggesting a unique role of SOPA1 in the fusion of mitochondrial inner membrane.

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

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Danyang Zhang ◽  
Yan Zhang ◽  
Jun Ma ◽  
Chunmei Zhu ◽  
Tongxin Niu ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Bound States ◽  
Proteolytic Processing ◽  
Power Stroke ◽  
Electron Microscopic ◽  
Inner Membrane ◽  
Hydrophobic Residues ◽  
Physiological Conditions ◽  
Mitochondrial Inner Membrane ◽  
Tube Expansion

Mammalian mitochondrial inner membrane fusion is mediated by optic atrophy 1 (OPA1). Under physiological conditions, OPA1 undergoes proteolytic processing to form a membrane-anchored long isoform (L-OPA1) and a soluble short isoform (S-OPA1). A combination of L-OPA1 and S-OPA1 is essential for efficient membrane fusion; however, the relevant mechanism is not well understood. In this study, we investigate the cryo-electron microscopic structures of S-OPA1–coated liposomes in nucleotide-free and GTPγS-bound states. S-OPA1 exhibits a general dynamin-like structure and can assemble onto membranes in a helical array with a dimer building block. We reveal that hydrophobic residues in its extended membrane-binding domain are critical for its tubulation activity. The binding of GTPγS triggers a conformational change and results in a rearrangement of the helical lattice and tube expansion similar to that of S-Mgm1. These observations indicate that S-OPA1 adopts a dynamin-like power stroke membrane remodeling mechanism during mitochondrial inner membrane fusion.

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 The essential yeast protein MIM44 (encoded by MPI1) is involved in an early step of preprotein translocation across the mitochondrial inner membrane.

1993 ◽  
Vol 13 (12) ◽  
pp. 7364-7371 ◽  
Author(s):  
J Blom ◽  
M Kübrich ◽  
J Rassow ◽  
W Voos ◽  
P J Dekker ◽  
...  
Keyword(s):  
Protein Import ◽  
Early Stage ◽  
Proteolytic Processing ◽  
Early Step ◽  
Direct Role ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Preprotein Translocation ◽  
In Transit

The essential yeast gene MPI1 encodes a mitochondrial membrane protein that is possibly involved in protein import into the organelle (A. C. Maarse, J. Blom, L. A. Grivell, and M. Meijer, EMBO J. 11:3619-3628, 1992). For this report, we determined the submitochondrial location of the MPI1 gene product and investigated whether it plays a direct role in the translocation of preproteins. By fractionation of mitochondria, the mature protein of 44 kDa was localized to the mitochondrial inner membrane and therefore termed MIM44. Import of the precursor of MIM44 required a membrane potential across the inner membrane and involved proteolytic processing of the precursor. A preprotein in transit across the mitochondrial membranes was cross-linked to MIM44, whereas preproteins arrested on the mitochondrial surface or fully imported proteins were not cross-linked. When preproteins were arrested at two distinct stages of translocation across the inner membrane, only preproteins at an early stage of translocation could be cross-linked to MIM44. Moreover, solubilized MIM44 was found to interact with in vitro-synthesized preproteins. We conclude that MIM44 is a component of the mitochondrial inner membrane import machinery and interacts with preproteins in an early step of translocation.

scholarly journals Role of mitochondrial inner membrane organizing system in protein biogenesis of the mitochondrial outer membrane

2012 ◽  
Vol 23 (20) ◽  
pp. 3948-3956 ◽  
Author(s):  
Maria Bohnert ◽  
Lena-Sophie Wenz ◽  
Ralf M. Zerbes ◽  
Susanne E. Horvath ◽  
David A. Stroud ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Early Stage ◽  
Outer Membrane Proteins ◽  
Mitochondrial Outer Membrane ◽  
Large Core ◽  
Large Protein ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Protein Biogenesis

Mitochondria contain two membranes, the outer membrane and the inner membrane with folded cristae. The mitochondrial inner membrane organizing system (MINOS) is a large protein complex required for maintaining inner membrane architecture. MINOS interacts with both preprotein transport machineries of the outer membrane, the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). It is unknown, however, whether MINOS plays a role in the biogenesis of outer membrane proteins. We have dissected the interaction of MINOS with TOM and SAM and report that MINOS binds to both translocases independently. MINOS binds to the SAM complex via the conserved polypeptide transport–associated domain of Sam50. Mitochondria lacking mitofilin, the large core subunit of MINOS, are impaired in the biogenesis of β-barrel proteins of the outer membrane, whereas mutant mitochondria lacking any of the other five MINOS subunits import β-barrel proteins in a manner similar to wild-type mitochondria. We show that mitofilin is required at an early stage of β-barrel biogenesis that includes the initial translocation through the TOM complex. We conclude that MINOS interacts with TOM and SAM independently and that the core subunit mitofilin is involved in biogenesis of outer membrane β-barrel proteins.

scholarly journals The J-related Segment of Tim44 Is Essential for Cell Viability: A Mutant Tim44 Remains in the Mitochondrial Import Site, but Inefficiently Recruits mtHsp70 and Impairs Protein Translocation

1999 ◽  
Vol 145 (5) ◽  
pp. 961-972 ◽  
Author(s):  
Alessio Merlin ◽  
Wolfgang Voos ◽  
Ammy C. Maarse ◽  
Michiel Meijer ◽  
Nikolaus Pfanner ◽  
...  
Keyword(s):  
Protein Import ◽  
Protein Translocation ◽  
Adaptor Protein ◽  
Dependent Manner ◽  
Wild Type ◽  
Yeast Saccharomyces Cerevisiae ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
J Proteins

Tim44 is a protein of the mitochondrial inner membrane and serves as an adaptor protein for mtHsp70 that drives the import of preproteins in an ATP-dependent manner. In this study we have modified the interaction of Tim44 with mtHsp70 and characterized the consequences for protein translocation. By deletion of an 18-residue segment of Tim44 with limited similarity to J-proteins, the binding of Tim44 to mtHsp70 was weakened. We found that in the yeast Saccharomyces cerevisiae the deletion of this segment is lethal. To investigate the role of the 18-residue segment, we expressed Tim44Δ18 in addition to the endogenous wild-type Tim44. Tim44Δ18 is correctly targeted to mitochondria and assembles in the inner membrane import site. The coexpression of Tim44Δ18 together with wild-type Tim44, however, does not stimulate protein import, but reduces its efficiency. In particular, the promotion of unfolding of preproteins during translocation is inhibited. mtHsp70 is still able to bind to Tim44Δ18 in an ATP-regulated manner, but the efficiency of interaction is reduced. These results suggest that the J-related segment of Tim44 is needed for productive interaction with mtHsp70. The efficient cooperation of mtHsp70 with Tim44 facilitates the translocation of loosely folded preproteins and plays a crucial role in the import of preproteins which contain a tightly folded domain.

scholarly journals Coassembly of Mgm1 isoforms requires cardiolipin and mediates mitochondrial inner membrane fusion

2009 ◽  
Vol 186 (6) ◽  
pp. 793-803 ◽  
Author(s):  
Rachel M. DeVay ◽  
Lenin Dominguez-Ramirez ◽  
Laura L. Lackner ◽  
Suzanne Hoppins ◽  
Henning Stahlberg ◽  
...  
Keyword(s):  
Membrane Fusion ◽  
Coiled Coil ◽  
Intermembrane Space ◽  
Dependent Manner ◽  
Related Protein ◽  
Mitochondrial Membranes ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
N Terminus ◽  
In Trans

Two dynamin-related protein (DRP) families are essential for fusion of the outer and inner mitochondrial membranes, Fzo1 (yeast)/Mfn1/Mfn2 (mammals) and Mgm1 (yeast)/Opa1 (mammals), respectively. Fzo1/Mfns possess two medial transmembrane domains, which place their critical GTPase and coiled-coil domains in the cytosol. In contrast, Mgm1/Opa1 are present in cells as long (l) isoforms that are anchored via the N terminus to the inner membrane, and short (s) isoforms were predicted to be soluble in the intermembrane space. We addressed the roles of Mgm1 isoforms and how DRPs function in membrane fusion. Our analysis indicates that in the absence of a membrane, l- and s-Mgm1 both exist as inactive GTPase monomers, but that together in trans they form a functional dimer in a cardiolipin-dependent manner that is the building block for higher-order assemblies.

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