scholarly journals Endophilin B1 is required for the maintenance of mitochondrial morphology

2004 ◽  
Vol 166 (7) ◽  
pp. 1027-1039 ◽  
Author(s):  
Mariusz Karbowski ◽  
Seon-Yong Jeong ◽  
Richard J. Youle
Keyword(s):  
Mitochondrial Membrane ◽  
Fatty Acyl ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Network ◽  
Truncated Protein ◽  
The Matrix ◽  
Membrane Compartment ◽  
Mitochondrial Distribution

We report that a fatty acyl transferase, endophilin B1, is required for maintenance of mitochondrial morphology. Down-regulation of this protein or overexpression of endophilin B1 lacking the NH2-terminal lipid-modifying domain causes striking alterations of the mitochondrial distribution and morphology. Dissociation of the outer mitochondrial membrane compartment from that of the matrix, and formation of vesicles and tubules of outer mitochondrial membrane, was also observed in both endophilin B1 knockdown cells and after overexpression of the truncated protein, indicating that endophilin B1 is required for the regulation of the outer mitochondrial membrane dynamics. We also show that endophilin B1 translocates to the mitochondria during the synchronous remodeling of the mitochondrial network that has been described to occur during apoptosis. Double knockdown of endophilin B1 and Drp1 leads to a mitochondrial phenotype identical to that of the Drp1 single knockdown, a result consistent with Drp1 acting upstream of endophilin B1 in the maintenance of morphological dynamics of mitochondria.

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 Calcium Deregulation and Mitochondrial Bioenergetics in GDAP1-Related CMT Disease

2019 ◽  
Vol 20 (2) ◽  
pp. 403 ◽  
Author(s):  
Paloma González-Sánchez ◽  
Jorgina Satrústegui ◽  
Francesc Palau ◽  
Araceli del Arco
Keyword(s):  
Mitochondrial Membrane ◽  
Energy Production ◽  
Mitochondrial Dynamics ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Network ◽  
Charcot Marie Tooth ◽  
Calcium Deregulation ◽  
Store Operated Calcium Entry ◽  
Mitochondrial Membrane Protein ◽  
Stimulation Of

The pathology of Charcot-Marie-Tooth (CMT), a disease arising from mutations in different genes, has been associated with an impairment of mitochondrial dynamics and axonal biology of mitochondria. Mutations in ganglioside-induced differentiation-associated protein 1 (GDAP1) cause several forms of CMT neuropathy, but the pathogenic mechanisms involved remain unclear. GDAP1 is an outer mitochondrial membrane protein highly expressed in neurons. It has been proposed to play a role in different aspects of mitochondrial physiology, including mitochondrial dynamics, oxidative stress processes, and mitochondrial transport along the axons. Disruption of the mitochondrial network in a neuroblastoma model of GDAP1-related CMT has been shown to decrease Ca2+ entry through the store-operated calcium entry (SOCE), which caused a failure in stimulation of mitochondrial respiration. In this review, we summarize the different functions proposed for GDAP1 and focus on the consequences for Ca2+ homeostasis and mitochondrial energy production linked to CMT disease caused by different GDAP1 mutations.

scholarly journals Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study

2013 ◽  
Vol 114 (2) ◽  
pp. 161-171 ◽  
Author(s):  
Martin Picard ◽  
Kathryn White ◽  
Douglass M. Turnbull
Keyword(s):  
Electron Microscopy ◽  
Skeletal Muscle ◽  
Mitochondrial Membrane ◽  
Freeze Fracture ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Mitochondrial Membranes ◽  
Intact Mouse ◽  
Mouse Skeletal Muscle

Dynamic remodeling of mitochondrial morphology through membrane dynamics are linked to changes in mitochondrial and cellular function. Although mitochondrial membrane fusion/fission events are frequent in cell culture models, whether mitochondrial membranes dynamically interact in postmitotic muscle fibers in vivo remains unclear. Furthermore, a quantitative assessment of mitochondrial morphology in intact muscle is lacking. Here, using electron microscopy (EM), we provide evidence of interacting membranes from adjacent mitochondria in intact mouse skeletal muscle. Electron-dense mitochondrial contact sites consistent with events of outer mitochondrial membrane tethering are also described. These data suggest that mitochondrial membranes interact in vivo among mitochondria, possibly to induce morphology transitions, for kiss-and-run behavior, or other processes involving contact between mitochondrial membranes. Furthermore, a combination of freeze-fracture scanning EM and transmission EM in orthogonal planes was used to characterize and quantify mitochondrial morphology. Two subpopulations of mitochondria were studied: subsarcolemmal (SS) and intermyofibrillar (IMF), which exhibited significant differences in morphological descriptors, including form factor (means ± SD for SS: 1.41 ± 0.45 vs. IMF: 2.89 ± 1.76, P < 0.01) and aspect ratio (1.97 ± 0.83 vs. 3.63 ± 2.13, P < 0.01) and circularity (0.75 ± 0.16 vs. 0.45 ± 0.22, P < 0.01) but not size (0.28 ± 0.31 vs. 0.27 ± 0.20 μm2). Frequency distributions for mitochondrial size and morphological parameters were highly skewed, suggesting the presence of mechanisms to influence mitochondrial size and shape. In addition, physical continuities between SS and IMF mitochondria indicated mixing of both subpopulations. These data provide evidence that mitochondrial membranes interact in vivo in mouse skeletal muscle and that factors may be involved in regulating skeletal muscle mitochondrial morphology.

scholarly journals Acute exercise remodels mitochondrial membrane interactions in mouse skeletal muscle

2013 ◽  
Vol 115 (10) ◽  
pp. 1562-1571 ◽  
Author(s):  
Martin Picard ◽  
Benoit J. Gentil ◽  
Meagan J. McManus ◽  
Kathryn White ◽  
Kyle St. Louis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mammalian Cells ◽  
Mitochondrial Membrane ◽  
Acute Exercise ◽  
Exercise Intervention ◽  
Cultured Cells ◽  
Mitochondrial Dynamics ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Membrane Interactions

A unique property of mitochondria in mammalian cells is their ability to physically interact and undergo dynamic events of fusion/fission that remodel their morphology and possibly their function. In cultured cells, metabolic perturbations similar to those incurred during exercise influence mitochondrial fusion and fission processes, but it is unknown whether exercise acutely alters mitochondrial morphology and/or membrane interactions in vivo. To study this question, we subjected mice to a 3-h voluntarily exercise intervention following their normal physical activity patterns, and quantified mitochondrial morphology and membrane interactions in the soleus using a quantitative electron microscopy approach. A single exercise bout effectively decreased blood glucose ( P < 0.05) and intramyocellular lipid content ( P < 0.01), indicating increased muscle metabolic demand. The number of mitochondria spanning Z-lines and proportion of electron-dense contact sites (EDCS) between adjacent mitochondrial membranes were increased immediately after exercise among both subsarcolemmal (+116%, P < 0.05) and intermyofibrillar mitochondria (+191%, P < 0.001), indicating increased physical interactions. Mitochondrial morphology, and abundance of the mitochondrial pro-fusion proteins Mfn2 and OPA1 were unchanged. Collectively, these results support the notion that mitochondrial membrane dynamics are actively remodelled in skeletal muscle, which may be regulated by contractile activity and the metabolic state. Future studies are required to understand the implications of mitochondrial dynamics in skeletal muscle physiology during exercise and inactivity.

scholarly journals Fission and fusion machineries converge at ER contact sites to regulate mitochondrial morphology

2020 ◽  
Vol 219 (4) ◽  
Author(s):  
Robert G. Abrisch ◽  
Samantha C. Gumbin ◽  
Brett Taylor Wisniewski ◽  
Laura L. Lackner ◽  
Gia K. Voeltz
Keyword(s):  
Steady State ◽  
Mitochondrial Fission ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Mitochondrial Network ◽  
Fusion Reactions ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Metabolic States ◽  
Membrane Contact

The steady-state morphology of the mitochondrial network is maintained by a balance of constitutive fission and fusion reactions. Disruption of this steady-state morphology results in either a fragmented or elongated network, both of which are associated with altered metabolic states and disease. How the processes of fission and fusion are balanced by the cell is unclear. Here we show that mitochondrial fission and fusion are spatially coordinated at ER membrane contact sites (MCSs). Multiple measures indicate that the mitochondrial fusion machinery, Mitofusins, accumulate at ER MCSs where fusion occurs. Furthermore, fission and fusion machineries colocalize to form hotspots for membrane dynamics at ER MCSs that can persist through sequential events. Because these hotspots can undergo fission and fusion, they have the potential to quickly respond to metabolic cues. Indeed, we discover that ER MCSs define the interface between polarized and depolarized segments of mitochondria and can rescue the membrane potential of damaged mitochondria by ER-associated fusion.

Emerging roles of mitochondrial membrane dynamics in health and disease

2009 ◽  
Vol 390 (8) ◽  
Author(s):  
Anja Schäfer ◽  
Andreas S. Reichert
Keyword(s):  
Quality Control ◽  
Molecular Basis ◽  
Mitochondrial Membrane ◽  
Mitochondrial Dynamics ◽  
Physiological Role ◽  
Membrane Dynamics ◽  
Mitochondrial Morphology ◽  
Mitochondrial Quality Control ◽  
Health And Disease

Abstract Mitochondria are highly dynamic organelles forming a tubular network that is sustained by fusion and fission events. Impairment thereof leads to various neuropathies in humans, such as optic atrophy and Parkinson's disease. We have only begun to understand the molecular machineries facilitating fusion and fission of mitochondria and how these processes are regulated. The physiological role of mitochondrial dynamics and how it may be involved in maintaining mitochondrial functionality is still unclear. Here, we discuss current views in this emerging field focusing on the molecular basis of how mitochondrial morphology is regulated and how this may contribute to mitochondrial quality control.

scholarly journals Molecular Integrity of Mitochondria Alters by Potassium Chloride

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Suman Mishra ◽  
Rajnikant Mishra
Keyword(s):  
Potassium Chloride ◽  
Mitochondrial Membrane ◽  
Protein Extraction ◽  
Electrostatic Force ◽  
Polyacrylamide Gel Electrophoresis ◽  
Matrix Proteins ◽  
Outer Mitochondrial Membrane ◽  
Mitochondrial Proteome ◽  
The Matrix ◽  
Mice Liver

Potassium chloride (KCl) has been commonly used in homogenization buffer and procedures of protein extraction. It is known to facilitate release of membrane-associated molecules but the higher concentration of KCl may affect the integrity of mitochondria by breaching the electrostatic force between the lipids and proteins. Therefore, it has been intended to explore the effect of KCl on mitochondrial proteome. The mitochondria were isolated from the mice liver and sub-fractionated into mitochondrial matrix and outer mitochondrial membrane fraction. The fractions were analysed by denaturing polyacrylamide gel electrophoresis (PAGE) and 2D-PAGE. The analysis of ultrastructure and protein profiles by MALDI-MS and data-mining reveals KCl-associated alterations in the integrity of mitochondria and its proteome. The mitochondrial membrane, cristae, and the matrix proteins appear altered under the influence of KCl.

Glucose metabolism in cancer cells: immunogold localization of hexokinase to the outer mitochondrial membrane

1995 ◽  
Vol 53 ◽  
pp. 1044-1045
Author(s):  
Krishan K. Arora ◽  
Glenn L. Decker ◽  
Peter L. Pedersen
Keyword(s):  
Tumor Cells ◽  
Mitochondrial Membrane ◽  
Present Report ◽  
Large Fraction ◽  
Mitochondrial Fraction ◽  
Immunogold Labeling ◽  
Outer Mitochondrial Membrane ◽  
Immunogold Localization ◽  
Hexokinase Activity ◽  
Normal Tissues

Hexokinase (ATP: D-hexose 6-phophotransferase EC 2.7.1.1) is the first enzyme of the glycolytic pathway which commits glucose to catabolism by catalyzing the phosphorylation of glucose with ATP. Previous studies have shown diat hexokinase activity is markedly elevated in rapidly growing tumor cells exhibiting high glucose catabolic rates. A large fraction (50-80%) of this enzyme activity is bound to the mitochondrial fraction (1,2) where it has preferred access to ATP (3). In contrast,the hexokinase activity of normal tissues is quite low, with one exception being brain which is a glucose-utilizing tissue (4). Biochemical evidence involving rigorous subfractionation studies have revealed striking differences between the subcellular distribution of hexokinase in normal and tumor cells [See review by Arora et al (4)].In the present report, we have utilized immunogold labeling techniques to evaluate die subcellular localization of hexokinase in highly glycolytic AS-30D hepatoma cells and in the tissue of its origin, i.e., rat liver.

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