scholarly journals Mitochondrial Membrane Remodeling

2022 ◽  
Vol 9 ◽  
Author(s):  
Ziyun Yang ◽  
Liang Wang ◽  
Cheng Yang ◽  
Shiming Pu ◽  
Ziqi Guo ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Membrane Remodeling ◽  
Mitochondrial Membranes ◽  
Functional Link ◽  
Cellular Processes ◽  
Mitochondrial Inner Membrane ◽  
Human Disorders ◽  
Specific Factors ◽  
Mitochondrial Morphogenesis ◽  
Architectural Organization

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.

scholarly journals Monolysocardiolipin (MLCL) interactions with mitochondrial membrane proteins

2020 ◽  
Vol 48 (3) ◽  
pp. 993-1004
Author(s):  
Anna L. Duncan
Keyword(s):  
Protein Interactions ◽  
Mitochondrial Membrane ◽  
Barth Syndrome ◽  
Mitochondrial Proteins ◽  
Mitochondrial Membranes ◽  
Inner Membrane ◽  
Computational Approaches ◽  
Mitochondrial Inner Membrane ◽  
Recent Developments ◽  
The Stability

Monolysocardiolipin (MLCL) is a three-tailed variant of cardiolipin (CL), the signature lipid of mitochondria. MLCL is not normally found in healthy tissue but accumulates in mitochondria of people with Barth syndrome (BTHS), with an overall increase in the MLCL:CL ratio. The reason for MLCL accumulation remains to be fully understood. The effect of MLCL build-up and decreased CL content in causing the characteristics of BTHS are also unclear. In both cases, an understanding of the nature of MLCL interaction with mitochondrial proteins will be key. Recent work has shown that MLCL associates less tightly than CL with proteins in the mitochondrial inner membrane, suggesting that MLCL accumulation is a result of CL degradation, and that the lack of MLCL–protein interactions compromises the stability of the protein-dense mitochondrial inner membrane, leading to a decrease in optimal respiration. There is some data on MLCL–protein interactions for proteins involved in the respiratory chain and in apoptosis, but there remains much to be understood regarding the nature of MLCL–protein interactions. Recent developments in structural, analytical and computational approaches mean that these investigations are now possible. Such an understanding will be key to further insights into how MLCL accumulation impacts mitochondrial membranes. In turn, these insights will help to support the development of therapies for people with BTHS and give a broader understanding of other diseases involving defective CL content.

scholarly journals Mitochondrial membrane potential regulates PINK1 import and proteolytic destabilization by PARL

2010 ◽  
Vol 191 (5) ◽  
pp. 933-942 ◽  
Author(s):  
Seok Min Jin ◽  
Michael Lazarou ◽  
Chunxin Wang ◽  
Lesley A. Kane ◽  
Derek P. Narendra ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Dopaminergic Neurons ◽  
Mammalian Cells ◽  
Mitochondrial Membrane ◽  
Mitochondrial Membranes ◽  
Rhomboid Protease ◽  
Mitochondrial Inner Membrane ◽  
Flight Muscles ◽  
And Function

PINK1 is a mitochondrial kinase mutated in some familial cases of Parkinson’s disease. It has been found to work in the same pathway as the E3 ligase Parkin in the maintenance of flight muscles and dopaminergic neurons in Drosophila melanogaster and to recruit cytosolic Parkin to mitochondria to mediate mitophagy in mammalian cells. Although PINK1 has a predicted mitochondrial import sequence, its cellular and submitochondrial localization remains unclear in part because it is rapidly degraded. In this study, we report that the mitochondrial inner membrane rhomboid protease presenilin-associated rhomboid-like protein (PARL) mediates cleavage of PINK1 dependent on mitochondrial membrane potential. In the absence of PARL, the constitutive degradation of PINK1 is inhibited, stabilizing a 60-kD form inside mitochondria. When mitochondrial membrane potential is dissipated, PINK1 accumulates as a 63-kD full-length form on the outer mitochondrial membrane, where it can recruit Parkin to impaired mitochondria. Thus, differential localization to the inner and outer mitochondrial membranes appears to regulate PINK1 stability and function.

scholarly journals A MicroRNA Signature of Hypoxia

2006 ◽  
Vol 27 (5) ◽  
pp. 1859-1867 ◽  
Author(s):  
Ritu Kulshreshtha ◽  
Manuela Ferracin ◽  
Sylwia E. Wojcik ◽  
Ramiro Garzon ◽  
Hansjuerg Alder ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Hypoxia Inducible Factor ◽  
Tumor Formation ◽  
Low Oxygen ◽  
Functional Link ◽  
Factors Affecting ◽  
Cellular Processes ◽  
Hypoxic Environment ◽  
Tumorigenic Transformation ◽  
First Time

ABSTRACT Recent research has identified critical roles for microRNAs in a large number of cellular processes, including tumorigenic transformation. While significant progress has been made towards understanding the mechanisms of gene regulation by microRNAs, much less is known about factors affecting the expression of these noncoding transcripts. Here, we demonstrate for the first time a functional link between hypoxia, a well-documented tumor microenvironment factor, and microRNA expression. Microarray-based expression profiles revealed that a specific spectrum of microRNAs (including miR-23, -24, -26, -27, -103, -107, -181, -210, and -213) is induced in response to low oxygen, at least some via a hypoxia-inducible-factor-dependent mechanism. Select members of this group (miR-26, -107, and -210) decrease proapoptotic signaling in a hypoxic environment, suggesting an impact of these transcripts on tumor formation. Interestingly, the vast majority of hypoxia-induced microRNAs are also overexpressed in a variety of human tumors.

scholarly journals Organization and sequence of the gene for the human mitochondrial dicarboxylate carrier: evolution of the carrier family

1999 ◽  
Vol 344 (3) ◽  
pp. 953-960 ◽  
Author(s):  
Giuseppe FIERMONTE ◽  
Vincenza DOLCE ◽  
Roberto ARRIGONI ◽  
Michael J. RUNSWICK ◽  
John E. WALKER ◽  
...  
Keyword(s):  
Mitochondrial Membrane ◽  
Cdna Sequence ◽  
Gene Sequence ◽  
Alu Sequences ◽  
Human Cdna ◽  
Mitochondrial Inner Membrane ◽  
Human Dna ◽  
Human Genes ◽  
Human Cdna Sequence ◽  
Liver And Kidney

The dicarboxylate carrier (DIC) is a nuclear-encoded protein located in the mitochondrial inner membrane. It catalyses the transport of dicarboxylates such as malate and succinate across the mitochondrial membrane in exchange for phosphate, sulphate and thiosulphate. We have determined the sequences of the human cDNA and gene for the DIC. The gene sequence was established from overlapping genomic clones generated by PCRs by use of primers and probes based upon the human cDNA sequence. It is spread over 8.6 kb of human DNA and is divided into 11 exons. Five short interspersed repetitive Alu sequences are found in intron I. The protein encoded by the gene is 287 amino acids long. In common with the rat protein, it does not have a processed presequence to help to target it into mitochondria. It has been demonstrated by Northern- and Western-blot analyses that the DIC is present in high amounts in liver and kidney, and at lower levels in all the other tissues analysed. The positions of introns contribute towards an understanding of the processes involved in the evolution of human genes for carrier proteins.

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.

Protein Quality Control Degradation in the Nucleus

2018 ◽  
Vol 87 (1) ◽  
pp. 725-749 ◽  
Author(s):  
Charisma Enam ◽  
Yifat Geffen ◽  
Tommer Ravid ◽  
Richard G. Gardner
Keyword(s):  
Quality Control ◽  
Protein Misfolding ◽  
Protein Quality ◽  
Current Knowledge ◽  
Protein Quality Control ◽  
Ubiquitin Proteasome System ◽  
Misfolded Proteins ◽  
Cellular Processes ◽  
Human Disorders ◽  
Protein Misfolding And Aggregation

Nuclear proteins participate in diverse cellular processes, many of which are essential for cell survival and viability. To maintain optimal nuclear physiology, the cell employs the ubiquitin-proteasome system to eliminate damaged and misfolded proteins in the nucleus that could otherwise harm the cell. In this review, we highlight the current knowledge about the major ubiquitin-protein ligases involved in protein quality control degradation (PQCD) in the nucleus and how they orchestrate their functions to eliminate misfolded proteins in different nuclear subcompartments. Many human disorders are causally linked to protein misfolding in the nucleus, hence we discuss major concepts that still need to be clarified to better understand the basis of the nuclear misfolded proteins’ toxic effects. Additionally, we touch upon potential strategies for manipulating nuclear PQCD pathways to ameliorate diseases associated with protein misfolding and aggregation in the nucleus.

Controllable membrane remodeling by a modified fragment of the apoptotic protein Bax

2020 ◽  
Author(s):  
Katherine G. Schaefer ◽  
Brayan Grau ◽  
Nicolas Moore ◽  
Ismael Mingarro ◽  
Gavin King ◽  
...  
Keyword(s):  
Membrane Remodeling ◽  
Intrinsic Apoptosis ◽  
Mitochondrial Membranes ◽  
Apoptotic Protein ◽  
Domain Protein

Intrinsic apoptosis is orchestrated by a group of proteins that mediate the coordinated disruption of mitochondrial membranes. Bax is a multi-domain protein that, upon activation, disrupts the integrity of the...

scholarly journals Molecular mechanism of mitochondrial phosphatidate transfer by Ups1

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Jiuwei Lu ◽  
Chun Chan ◽  
Leiye Yu ◽  
Jun Fan ◽  
Fei Sun ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Mitochondrial Membrane ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Membranes ◽  
Inner Mitochondrial Membrane ◽  
Membrane Interaction ◽  
Detailed Mechanism ◽  
Physiological Regulator ◽  
Membrane Bound ◽  
Dynamics Simulations

AbstractCardiolipin, an essential mitochondrial physiological regulator, is synthesized from phosphatidic acid (PA) in the inner mitochondrial membrane (IMM). PA is synthesized in the endoplasmic reticulum and transferred to the IMM via the outer mitochondrial membrane (OMM) under mediation by the Ups1/Mdm35 protein family. Despite the availability of numerous crystal structures, the detailed mechanism underlying PA transfer between mitochondrial membranes remains unclear. Here, a model of Ups1/Mdm35-membrane interaction is established using combined crystallographic data, all-atom molecular dynamics simulations, extensive structural comparisons, and biophysical assays. The α2-loop, L2-loop, and α3 helix of Ups1 mediate membrane interactions. Moreover, non-complexed Ups1 on membranes is found to be a key transition state for PA transfer. The membrane-bound non-complexed Ups1/ membrane-bound Ups1 ratio, which can be regulated by environmental pH, is inversely correlated with the PA transfer activity of Ups1/Mdm35. These results demonstrate a new model of the fine conformational changes of Ups1/Mdm35 during PA transfer.

scholarly journals Regulating ENaC’s gate

2020 ◽  
Vol 318 (1) ◽  
pp. C150-C162 ◽  
Author(s):  
Thomas R. Kleyman ◽  
Douglas C. Eaton
Keyword(s):  
Cleavage Sites ◽  
Open Probability ◽  
Protease Cleavage ◽  
Inositol Phospholipids ◽  
Human Disorders ◽  
Protease Cleavage Sites ◽  
Specific Factors ◽  
The Impact ◽  
Channel Transition ◽  
Extracellular Environment

Epithelial Na+ channels (ENaCs) are members of a family of cation channels that function as sensors of the extracellular environment. ENaCs are activated by specific proteases in the biosynthetic pathway and at the cell surface and remove embedded inhibitory tracts, which allows channels to transition to higher open-probability states. Resolved structures of ENaC and an acid-sensing ion channel revealed highly organized extracellular regions. Within the periphery of ENaC subunits are unique domains formed by antiparallel β-strands containing the inhibitory tracts and protease cleavage sites. ENaCs are inhibited by Na+ binding to specific extracellular site(s), which promotes channel transition to a lower open-probability state. Specific inositol phospholipids and channel modification by Cys-palmitoylation enhance channel open probability. How these regulatory factors interact in a concerted manner to influence channel open probability is an important question that has not been resolved. These various factors are reviewed, and the impact of specific factors on human disorders is discussed.

scholarly journals MAVS ‐induced mitochondrial membrane remodeling

FEBS Journal ◽  
2019 ◽  
Vol 286 (8) ◽  
pp. 1540-1542 ◽  
Author(s):  
Hector Flores‐Romero ◽  
Ana J. García‐Sáez
Keyword(s):  
Mitochondrial Membrane ◽  
Membrane Remodeling
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