scholarly journals Myofibril and mitochondria morphogenesis are coordinated by a mechanical feedback mechanism in muscle

2020 ◽  
Author(s):  
Jerome Avellaneda ◽  
Clement Rodier ◽  
Fabrice Daian ◽  
Thomas Rival ◽  
Nuno Miguel Luis ◽  
...  
Keyword(s):  
Striated Muscle ◽  
Flight Muscle ◽  
Mitochondrial Dynamics ◽  
Feedback Mechanism ◽  
Mitochondrial Fusion ◽  
Striated Muscles ◽  
Sarcomeric Proteins ◽  
Muscle Type ◽  
Flight Muscles ◽  
Mechanical Feedback

AbstractComplex animals build specialised muscle to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres as well as mitochondria are muscle type specific. However, mechanisms coordinating mitochondria with sarcomere morphogenesis are elusive. Here we use Drosophila muscles to demonstrate that myofibril and mitochondria morphogenesis are intimately linked. In flight muscles, the muscle selector spalt instructs mitochondria to intercalate between myofibrils, which in turn mechanically constrain mitochondria into elongated shapes. Conversely in cross-striated muscles, mitochondria networks surround myofibril bundles, contacting myofibrils only with thin extensions. To investigate the mechanism causing these differences, we manipulated mitochondrial dynamics and found that increased mitochondrial fusion during myofibril assembly prevents mitochondrial intercalation in flight muscles. Strikingly, this coincides with the expression of cross-striated muscle specific sarcomeric proteins. Consequently, flight muscle myofibrils convert towards a partially cross-striated architecture. Together, these data suggest a biomechanical feedback mechanism downstream of spalt synchronizing mitochondria with myofibril morphogenesis.

scholarly journals Myofibril and mitochondria morphogenesis are coordinated by a mechanical feedback mechanism in muscle

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jerome Avellaneda ◽  
Clement Rodier ◽  
Fabrice Daian ◽  
Nicolas Brouilly ◽  
Thomas Rival ◽  
...  
Keyword(s):  
Striated Muscle ◽  
Flight Muscle ◽  
Mitochondrial Dynamics ◽  
Feedback Mechanism ◽  
Mitochondrial Fusion ◽  
Sarcomeric Proteins ◽  
Muscle Type ◽  
Leg Muscles ◽  
Flight Muscles ◽  
Mechanical Feedback

AbstractComplex animals build specialised muscles to match specific biomechanical and energetic needs. Hence, composition and architecture of sarcomeres and mitochondria are muscle type specific. However, mechanisms coordinating mitochondria with sarcomere morphogenesis are elusive. Here we use Drosophila muscles to demonstrate that myofibril and mitochondria morphogenesis are intimately linked. In flight muscles, the muscle selector spalt instructs mitochondria to intercalate between myofibrils, which in turn mechanically constrain mitochondria into elongated shapes. Conversely in cross-striated leg muscles, mitochondria networks surround myofibril bundles, contacting myofibrils only with thin extensions. To investigate the mechanism causing these differences, we manipulated mitochondrial dynamics and found that increased mitochondrial fusion during myofibril assembly prevents mitochondrial intercalation in flight muscles. Strikingly, this causes the expression of cross-striated muscle specific sarcomeric proteins. Consequently, flight muscle myofibrils convert towards a partially cross-striated architecture. Together, these data suggest a biomechanical feedback mechanism downstream of spalt synchronizing mitochondria with myofibril morphogenesis.

scholarly journals CryoEM structure of Drosophila flight muscle thick filaments at 7 Å resolution

2020 ◽  
Vol 3 (8) ◽  
pp. e202000823
Author(s):  
Nadia Daneshparvar ◽  
Dianne W Taylor ◽  
Thomas S O’Leary ◽  
Hamidreza Rahmani ◽  
Fatemeh Abbasiyeganeh ◽  
...  
Keyword(s):  
Striated Muscle ◽  
Flight Muscle ◽  
Myosin Ii ◽  
Coiled Coil ◽  
Fruit Fly ◽  
Actin Binding ◽  
Thick Filaments ◽  
Flight Muscles ◽  
Lethocerus Indicus ◽  
Globular Head

Striated muscle thick filaments are composed of myosin II and several non-myosin proteins. Myosin II’s long α-helical coiled-coil tail forms the dense protein backbone of filaments, whereas its N-terminal globular head containing the catalytic and actin-binding activities extends outward from the backbone. Here, we report the structure of thick filaments of the flight muscle of the fruit fly Drosophila melanogaster at 7 Å resolution. Its myosin tails are arranged in curved molecular crystalline layers identical to flight muscles of the giant water bug Lethocerus indicus. Four non-myosin densities are observed, three of which correspond to ones found in Lethocerus; one new density, possibly stretchin-mlck, is found on the backbone outer surface. Surprisingly, the myosin heads are disordered rather than ordered along the filament backbone. Our results show striking myosin tail similarity within flight muscle filaments of two insect orders separated by several hundred million years of evolution.

scholarly journals CryoEM Structure of Drosophila Flight Muscle Thick Filaments at 7Å Resolution

2020 ◽  
Author(s):  
Nadia Daneshparvar ◽  
Dianne W. Taylor ◽  
Thomas S. O’Leary ◽  
Hamidreza Rahmani ◽  
Fatemeh Abbasi Yeganeh ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Striated Muscle ◽  
Flight Muscle ◽  
Coiled Coil ◽  
Thick Filament ◽  
Fruit Fly ◽  
Actin Binding ◽  
Thick Filaments ◽  
Flight Muscles ◽  
Lethocerus Indicus

AbstractStriated muscle thick filaments are composed of myosin II and several non-myosin proteins. Myosin II’s long α-helical coiled-coil tail forms the dense protein backbone of filaments while its N-terminal globular head containing the catalytic and actin binding activities extends outward from the backbone. Here we report the structure of thick filaments of the flight muscle of the fruit fly Drosophila melanogaster at 7 Å resolution. Its myosin tails are arranged in curved molecular crystalline layers identical to flight muscles of the giant waterbug Lethocerus indicus. Four non-myosin densities are observed, three of which correspond to ones found in Lethocerus; one new density, possibly stretchin-Mlck, is found on the backbone outer surface. Surprisingly, the myosin heads are disordered rather than ordered along the filament backbone. Our results show striking myosin tail similarity within flight muscle filaments of two insect orders separated by several hundred million years of evolution.Significance StatementMyosin thick filaments are one of striated muscle’s key structures, but also one of its least understood. A key question is how the myosin a-helical coiled-coil tail is arranged in the backbone. At 7Å resolution, sufficient to resolve individual a-helices, the myosin tail arrangement in thick filaments from the flight muscle of the fruit fly Drosophila melanogaster is strikingly similar to the myosin tail arrangement in flight muscles of the giant waterbug Lethocerus indicus. Nearly every other thick filament feature is different. Drosophila and Lethocerus evolved separately >245 million years ago suggesting myosin tail packing into curved molecular crystalline layers forms a highly conserved thick filament building block and different properties are obtained by alterations in non-myosin proteins.

scholarly journals Glucose limitation activates AMPK coupled SENP1-Sirt3 signalling in mitochondria for T cell memory development

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jianli He ◽  
Xun Shangguan ◽  
Wei Zhou ◽  
Ying Cao ◽  
Quan Zheng ◽  
...  
Keyword(s):  
T Cell ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fusion ◽  
Metabolic Reprogramming ◽  
Negative Regulator ◽  
T Cell Memory ◽  
Memory Development ◽  
Cell Memory ◽  
Glucose Limitation ◽  
Glycolytic Intermediate

AbstractMetabolic programming and mitochondrial dynamics along with T cell differentiation affect T cell fate and memory development; however, how to control metabolic reprogramming and mitochondrial dynamics in T cell memory development is unclear. Here, we provide evidence that the SUMO protease SENP1 promotes T cell memory development via Sirt3 deSUMOylation. SENP1-Sirt3 signalling augments the deacetylase activity of Sirt3, promoting both OXPHOS and mitochondrial fusion. Mechanistically, SENP1 activates Sirt3 deacetylase activity in T cell mitochondria, leading to reduction of the acetylation of mitochondrial metalloprotease YME1L1. Consequently, deacetylation of YME1L1 suppresses its activity on OPA1 cleavage to facilitate mitochondrial fusion, which results in T cell survival and promotes T cell memory development. We also show that the glycolytic intermediate fructose-1,6-bisphosphate (FBP) as a negative regulator suppresses AMPK-mediated activation of the SENP1-Sirt3 axis and reduces memory development. Moreover, glucose limitation reduces FBP production and activates AMPK during T cell memory development. These data show that glucose limitation activates AMPK and the subsequent SENP1-Sirt3 signalling for T cell memory development.

scholarly journals When the Balance Tips: Dysregulation of Mitochondrial Dynamics as a Culprit in Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 4617
Author(s):  
Styliana Kyriakoudi ◽  
Anthi Drousiotou ◽  
Petros P. Petrou
Keyword(s):  
Insulin Resistance ◽  
Mitochondrial Function ◽  
Human Disease ◽  
Molecular Mechanisms ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fusion ◽  
Mitochondrial Morphology ◽  
Disease Development ◽  
Pathological Conditions ◽  
Wide Range

Mitochondria are dynamic organelles, the morphology of which is tightly linked to their functions. The interplay between the coordinated events of fusion and fission that are collectively described as mitochondrial dynamics regulates mitochondrial morphology and adjusts mitochondrial function. Over the last few years, accruing evidence established a connection between dysregulated mitochondrial dynamics and disease development and progression. Defects in key components of the machinery mediating mitochondrial fusion and fission have been linked to a wide range of pathological conditions, such as insulin resistance and obesity, neurodegenerative diseases and cancer. Here, we provide an update on the molecular mechanisms promoting mitochondrial fusion and fission in mammals and discuss the emerging association of disturbed mitochondrial dynamics with human disease.

scholarly journals Interleukin-1β mediates alterations in mitochondrial fusion/fission proteins and memory impairment induced by amyloid-β oligomers

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Andre F. Batista ◽  
Tayná Rody ◽  
Leticia Forny-Germano ◽  
Suzana Cerdeiro ◽  
Maria Bellio ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mitochondrial Dysfunction ◽  
Memory Impairment ◽  
Mitochondrial Dynamics ◽  
Interleukin 1 ◽  
Amyloid Β ◽  
Mitochondrial Fusion ◽  
Synapse Loss ◽  
Cynomolgus Macaques ◽  
The Impact

Abstract Background The lack of effective treatments for Alzheimer’s disease (AD) reflects an incomplete understanding of disease mechanisms. Alterations in proteins involved in mitochondrial dynamics, an essential process for mitochondrial integrity and function, have been reported in AD brains. Impaired mitochondrial dynamics causes mitochondrial dysfunction and has been associated with cognitive impairment in AD. Here, we investigated a possible link between pro-inflammatory interleukin-1 (IL-1), mitochondrial dysfunction, and cognitive impairment in AD models. Methods We exposed primary hippocampal cell cultures to amyloid-β oligomers (AβOs) and carried out AβO infusions into the lateral cerebral ventricle of cynomolgus macaques to assess the impact of AβOs on proteins that regulate mitochondrial dynamics. Where indicated, primary cultures were pre-treated with mitochondrial division inhibitor 1 (mdivi-1), or with anakinra, a recombinant interleukin-1 receptor (IL-1R) antagonist used in the treatment of rheumatoid arthritis. Cognitive impairment was investigated in C57BL/6 mice that received an intracerebroventricular (i.c.v.) infusion of AβOs in the presence or absence of mdivi-1. To assess the role of interleukin-1 beta (IL-1β) in AβO-induced alterations in mitochondrial proteins and memory impairment, interleukin receptor-1 knockout (Il1r1−/−) mice received an i.c.v. infusion of AβOs. Results We report that anakinra prevented AβO-induced alteration in mitochondrial dynamics proteins in primary hippocampal cultures. Altered levels of proteins involved in mitochondrial fusion and fission were observed in the brains of cynomolgus macaques that received i.c.v. infusions of AβOs. The mitochondrial fission inhibitor, mdivi-1, alleviated synapse loss and cognitive impairment induced by AβOs in mice. In addition, AβOs failed to cause alterations in expression of mitochondrial dynamics proteins or memory impairment in Il1r1−/− mice. Conclusion These findings indicate that IL-1β mediates the impact of AβOs on proteins involved in mitochondrial dynamics and that strategies aimed to prevent pathological alterations in those proteins may counteract synapse loss and cognitive impairment in AD.

scholarly journals Characterization of components of Z-bands in the fibrillar flight muscle of Drosophila melanogaster.

1989 ◽  
Vol 109 (5) ◽  
pp. 2157-2167 ◽  
Author(s):  
J D Saide ◽  
S Chin-Bow ◽  
J Hogan-Sheldon ◽  
L Busquets-Turner ◽  
J O Vigoreaux ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Monoclonal Antibodies ◽  
Flight Muscle ◽  
Cross Reactivity ◽  
Antigenic Determinants ◽  
Immunogold Staining ◽  
Thick Filaments ◽  
The Matrix ◽  
Flight Muscles

Twelve monoclonal antibodies have been raised against proteins in preparations of Z-disks isolated from Drosophila melanogaster flight muscle. The monoclonal antibodies that recognized Z-band components were identified by immunofluorescence microscopy of flight muscle myofibrils. These antibodies have identified three Z-disk antigens on immunoblots of myofibrillar proteins. Monoclonal antibodies alpha:1-4 recognize a 90-100-kD protein which we identify as alpha-actinin on the basis of cross-reactivity with antibodies raised against honeybee and vertebrate alpha-actinins. Monoclonal antibodies P:1-4 bind to the high molecular mass protein, projectin, a component of connecting filaments that link the ends of thick filaments to the Z-band in insect asynchronous flight muscles. The anti-projectin antibodies also stain synchronous muscle, but, surprisingly, the epitopes here are within the A-bands, not between the A- and Z-bands, as in flight muscle. Monoclonal antibodies Z(210):1-4 recognize a 210-kD protein that has not been previously shown to be a Z-band structural component. A fourth antigen, resolved as a doublet (approximately 400/600 kD) on immunoblots of Drosophila fibrillar proteins, is detected by a cross reacting antibody, Z(400):2, raised against a protein in isolated honeybee Z-disks. On Lowicryl sections of asynchronous flight muscle, indirect immunogold staining has localized alpha-actinin and the 210-kD protein throughout the matrix of the Z-band, projectin between the Z- and A-bands, and the 400/600-kD components at the I-band/Z-band junction. Drosophila alpha-actinin, projectin, and the 400/600-kD components share some antigenic determinants with corresponding honeybee proteins, but no honeybee protein interacts with any of the Z(210) antibodies.

scholarly journals Dynamin-related protein 1 deficiency accelerates lipopolysaccharide-induced acute liver injury and inflammation in mice

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Lixiang Wang ◽  
Xin Li ◽  
Yuki Hanada ◽  
Nao Hasuzawa ◽  
Yoshinori Moriyama ◽  
...  
Keyword(s):  
Liver Disease ◽  
Liver Injury ◽  
Er Stress ◽  
Disease Progression ◽  
Acute Liver Injury ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Related Protein ◽  
Liver Disease Progression

AbstractMitochondrial fusion and fission, which are strongly related to normal mitochondrial function, are referred to as mitochondrial dynamics. Mitochondrial fusion defects in the liver cause a non-alcoholic steatohepatitis-like phenotype and liver cancer. However, whether mitochondrial fission defect directly impair liver function and stimulate liver disease progression, too, is unclear. Dynamin-related protein 1 (DRP1) is a key factor controlling mitochondrial fission. We hypothesized that DRP1 defects are a causal factor directly involved in liver disease development and stimulate liver disease progression. Drp1 defects directly promoted endoplasmic reticulum (ER) stress, hepatocyte death, and subsequently induced infiltration of inflammatory macrophages. Drp1 deletion increased the expression of numerous genes involved in the immune response and DNA damage in Drp1LiKO mouse primary hepatocytes. We administered lipopolysaccharide (LPS) to liver-specific Drp1-knockout (Drp1LiKO) mice and observed an increased inflammatory cytokine expression in the liver and serum caused by exaggerated ER stress and enhanced inflammasome activation. This study indicates that Drp1 defect-induced mitochondrial dynamics dysfunction directly regulates the fate and function of hepatocytes and enhances LPS-induced acute liver injury in vivo.

Phylogenetic implications of the superfast myosin in extraocular muscles

2002 ◽  
Vol 205 (15) ◽  
pp. 2189-2201 ◽  
Author(s):  
Fred Schachat ◽  
Margaret M. Briggs
Keyword(s):  
Myosin Heavy Chain ◽  
Gene Cluster ◽  
Heavy Chain ◽  
Striated Muscle ◽  
Extraocular Muscles ◽  
Chromosome 17 ◽  
Striated Muscles ◽  
Chromosome 11 ◽  
Phylogenetic Implications ◽  
Myh Gene

SUMMARY Extraocular muscle exhibits higher-velocity and lower-tension contractions than other vertebrate striated muscles. These distinctive physiological properties are associated with the expression of a novel extraocular myosin heavy chain (MYH). Encoded by the MYH13 gene, the extraocular myosin heavy chain is a member of the fast/developmental MYH gene cluster on human chromosome 17 and the syntenic MYH cluster on mouse chromosome 11. Comparison of cDNA sequences reveals that MYH13 also encodes the atypical MYH identified in laryngeal muscles, which have similar fast contractile properties. Comparing the MYH13 sequence with the other members of the fast/developmental cluster, the slow/cardiac MYH genes and two orphan skeletal MYH genes in the human genome provides insights into the origins of specialization in striated muscle myosins. Specifically, these studies indicate (i) that the extraocular myosin is not derived from the adult fast skeletal muscle myosins, but was the first member of the fast/developmental MYH gene cluster to diverge and specialize, (ii) that the motor and rod domains of the MYH13 have evolved under different selective pressures and (iii) that the MYH13 gene has been largely insulated from genomic events that have shaped other members of the fast/developmental cluster. In addition, phylogenetic footprinting suggests that regulation of the extraocular MYH gene is not governed primarily by myogenic factors, but by a hierarchical network of regulatory factors that relate its expression to the development of extraocular muscles.

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