scholarly journals The 3D Organisation of Mitochondria in Primate Photoreceptors

2021 ◽  
Author(s):  
Matthew J Hayes ◽  
Dhani Tracey-White ◽  
Jaimie Hoh Kam ◽  
Michael B Powner ◽  
Glen Jeffery
Keyword(s):  
Macaca Fascicularis ◽  
Mitochondrial Fission ◽  
3D Structure ◽  
Rods And Cones ◽  
Mitochondrial Inner Membrane ◽  
Large Numbers ◽  
Healthy State ◽  
Block Face ◽  
Membrane Contact ◽  
Rod And Cone Photoreceptors

Abstract Vertebrate photoreceptors contain large numbers of closely-packed mitochondria which sustain the high metabolic demands of these cells. These mitochondria populations are dynamic and undergo fusion and fission events. This activity serves to maintain the population in a healthy state. In the event of mitochondrial damage, sub-domains, or indeed whole mitochondria, can be degraded and population homeostasis achieved. If this process is overwhelmed cell death may result. Death of photoreceptors contributes to loss of vision in aging individuals and is associated with many eye diseases. In this study we used serial block face scanning electron microscopy of adult (Macaca fascicularis) retinae to examine the 3D structure of mitochondria in rod and cone photoreceptors. Healthy-looking photoreceptors contain mitochondria with a range of shapes which are associated with different regions of the cell. In some photoreceptors we observe mitochondrial swelling and other changes we associate with stress or degeneration of the cell. In both rods and cones we identify elongated domains of mitochondria with densely-packed normal cristae associated with photoreceptor ciliary rootlet bundles. We observe mitochondrial fission and mitochondrion fragments localised to these domains. Swollen mitochondria with few intact cristae are located towards the periphery of the photoreceptor inner-segment in rods, whilst they are found throughout the cell in cones. Swollen mitochondria exhibit sites on the mitochondrial inner membrane which have undergone complex invagination resulting in membranous, electron-dense aggregates. Membrane contact occurs between the mitochondrion and the photoreceptor plasma membrane in the vicinity of these aggregates, and a series of subsequent membrane fusions results in expulsion of the mitochondrial aggregate from the photoreceptor. These events are primarily associated with rods, likely reflecting the ageing mechanism in primates where many rods die but cones do not. Possible consequences of this atypical mitochondrial degradation are discussed.

scholarly journals The 3D organisation of mitochondria in primate photoreceptors

2021 ◽  
Author(s):  
Matthew J Hayes ◽  
Dhani Tracey-White ◽  
Jaimie Hoh Kam ◽  
Michael B Powner ◽  
Glen J Jeffery
Keyword(s):  
Macaca Fascicularis ◽  
Mitochondrial Fission ◽  
3D Structure ◽  
Rods And Cones ◽  
Mitochondrial Inner Membrane ◽  
Large Numbers ◽  
Healthy State ◽  
Block Face ◽  
Membrane Contact ◽  
Rod And Cone Photoreceptors

Vertebrate photoreceptors contain large numbers of closely-packed mitochondria which sustain the high metabolic demands of these cells. These mitochondria populations are dynamic and undergo fusion and fission events. This activity serves to maintain the population in a healthy state. In the event of mitochondrial damage, sub-domains, or indeed whole mitochondria, can be degraded and population homeostasis achieved. If this process is overwhelmed cell death may result. Death of photoreceptors contributes to loss of vision in aging individuals and is associated with many eye diseases. In this study we used serial block face scanning electron microscopy of adult (Macaca fascicularis) retinae to examine the 3D structure of mitochondria in rod and cone photoreceptors. Healthy-looking photoreceptors contain mitochondria with a range of shapes which are associated with different regions of the cell. In some photoreceptors we observe mitochondrial swelling and other changes we associate with stress or degeneration of the cell. In both rods and cones we identify elongated domains of mitochondria with densely-packed normal cristae associated with photoreceptor ciliary rootlet bundles. We observe mitochondrial fission and mitochondrion fragments localised to these domains. Swollen mitochondria with few intact cristae are located towards the periphery of the photoreceptor inner-segment in rods, whilst they are found throughout the cell in cones. Swollen mitochondria exhibit sites on the mitochondrial inner membrane which have undergone complex invagination resulting in membranous, electron-dense aggregates. Membrane contact occurs between the mitochondrion and the photoreceptor plasma membrane in the vicinity of these aggregates, and a series of subsequent membrane fusions results in expulsion of the mitochondrial aggregate from the photoreceptor. These events are primarily associated with rods, likely reflecting the ageing mechanism in primates where many rods die but cones do not. Possible consequences of this atypical mitochondrial degradation are discussed.

scholarly journals The 3D organisation of mitochondria in primate photoreceptors

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthew J. Hayes ◽  
Dhani Tracey-White ◽  
Jaimie Hoh Kam ◽  
Michael B. Powner ◽  
Glen Jeffery
Keyword(s):  
Retinal Pigment ◽  
Mitochondrial Fission ◽  
3D Structure ◽  
Rods And Cones ◽  
Mitochondrial Inner Membrane ◽  
Large Numbers ◽  
Healthy State ◽  
Block Face ◽  
Membrane Contact ◽  
Rod And Cone Photoreceptors

AbstractVertebrate photoreceptors contain large numbers of closely-packed mitochondria which sustain the high metabolic demands of these cells. These mitochondria populations are dynamic and undergo fusion and fission events. This activity serves to maintain the population in a healthy state. In the event of mitochondrial damage, sub-domains, or indeed whole mitochondria, can be degraded and population homeostasis achieved. If this process is overwhelmed cell death may result. Death of photoreceptors contributes to loss of vision in aging individuals and is associated with many eye diseases. In this study we used serial block face scanning electron microscopy of adult Macaca fascicularis retinae to examine the 3D structure of mitochondria in rod and cone photoreceptors. We show that healthy-looking photoreceptors contain mitochondria exhibiting a range of shapes which are associated with different regions of the cell. In some photoreceptors we observe mitochondrial swelling and other changes often associated with cellular stress. In rods and cones that appear stressed we identify elongated domains of mitochondria with densely-packed normal cristae associated with photoreceptor ciliary rootlet bundles. We observe mitochondrial fission and mitochondrion fragments localised to these domains. Swollen mitochondria with few intact cristae are located towards the periphery of the photoreceptor inner-segment in rods, whilst they are found throughout the cell in cones. Swollen mitochondria exhibit sites on the mitochondrial inner membrane which have undergone complex invagination resulting in membranous, electron-dense aggregates. Membrane contact occurs between the mitochondrion and the photoreceptor plasma membrane in the vicinity of these aggregates, and a series of subsequent membrane fusions results in expulsion of the mitochondrial aggregate from the photoreceptor. These events are primarily associated with rods. The potential fate of this purged material and consequences of its clearance by retinal pigment epithelia are discussed.

scholarly journals The potential mechanism of mitochondrial dysfunction in septic cardiomyopathy

2018 ◽  
Vol 46 (6) ◽  
pp. 2157-2169 ◽  
Author(s):  
Pan Pan ◽  
Xiaoting Wang ◽  
Dawei Liu
Keyword(s):  
Mitochondrial Function ◽  
Mitochondrial Gene ◽  
Mitochondrial Fission ◽  
Organ Damage ◽  
Septic Cardiomyopathy ◽  
Mitochondrial Uncoupling ◽  
Heart Research ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Proton Leakage

Septic cardiomyopathy is one of the most serious complications of sepsis or septic shock. Basic and clinical research has studied the mechanism of cardiac dysfunction for more than five decades. It has become clear that myocardial depression is not related to hypoperfusion. As the heart is highly dependent on abundant adenosine triphosphate (ATP) levels to maintain its contraction and diastolic function, impaired mitochondrial function is lethally detrimental to the heart. Research has shown that mitochondria play an important role in organ damage during sepsis. The mitochondria-related mechanisms in septic cardiomyopathy have been discussed in terms of restoring mitochondrial function. Mitochondrial uncoupling proteins located in the mitochondrial inner membrane can promote proton leakage across the mitochondrial inner membrane. Recent studies have demonstrated that proton leakage is the essential regulator of mitochondrial membrane potential and the generation of reactive oxygen species (ROS) and ATP. Other mechanisms involved in septic cardiomyopathy include mitochondrial ROS production and oxidative stress, mitochondria Ca2+ handling, mitochondrial DNA in sepsis, mitochondrial fission and fusion, mitochondrial biogenesis, mitochondrial gene regulation and mitochondria autophagy. This review will provide an overview of recent insights into the factors contributing to septic cardiomyopathy.

scholarly journals Uniform nomenclature for the mitochondrial contact site and cristae organizing system

2014 ◽  
Vol 204 (7) ◽  
pp. 1083-1086 ◽  
Author(s):  
Nikolaus Pfanner ◽  
Martin van der Laan ◽  
Paolo Amati ◽  
Roderick A. Capaldi ◽  
Amy A. Caudy ◽  
...  
Keyword(s):  
Large Protein ◽  
Contact Site ◽  
Inner Membrane ◽  
Future Studies ◽  
Membrane Contact Sites ◽  
Contact Sites ◽  
Mitochondrial Inner Membrane ◽  
Large Protein Complex ◽  
Membrane Contact ◽  
Uniform Nomenclature

The mitochondrial inner membrane contains a large protein complex that functions in inner membrane organization and formation of membrane contact sites. The complex was variably named the mitochondrial contact site complex, mitochondrial inner membrane organizing system, mitochondrial organizing structure, or Mitofilin/Fcj1 complex. To facilitate future studies, we propose to unify the nomenclature and term the complex “mitochondrial contact site and cristae organizing system” and its subunits Mic10 to Mic60.

scholarly journals Dynamin-related Protein 1 (Drp1) Promotes Structural Intermediates of Membrane Division

2014 ◽  
Vol 289 (44) ◽  
pp. 30645-30656 ◽  
Author(s):  
Begoña Ugarte-Uribe ◽  
Hans-Michael Müller ◽  
Miki Otsuki ◽  
Walter Nickel ◽  
Ana J. García-Sáez
Keyword(s):  
Self Assembly ◽  
Membrane Lipids ◽  
Mitochondrial Fission ◽  
Gtp Hydrolysis ◽  
Fluorescence Confocal Microscopy ◽  
Membrane Tethering ◽  
Membrane Tubulation ◽  
Membrane Contact ◽  
Membrane Division ◽  
Flat Membranes

Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. Despite the link between Drp1 malfunction and human disease, the molecular details of its membrane activity remain poorly understood. Here we reconstituted and directly visualized Drp1 activity in giant unilamellar vesicles. We quantified the effect of lipid composition and GTP on membrane binding and remodeling activity by fluorescence confocal microscopy and flow cytometry. In contrast to other dynamin relatives, Drp1 bound to both curved and flat membranes even in the absence of nucleotides. We also found that Drp1 induced membrane tubulation that was stimulated by cardiolipin. Moreover, Drp1 promoted membrane tethering dependent on the intrinsic curvature of the membrane lipids and on GTP. Interestingly, Drp1 concentrated at membrane contact surfaces and, in the presence of GTP, formed discrete clusters on the vesicles. Our findings support a role of Drp1 not only in the formation of lipid tubes but also on the stabilization of tightly apposed membranes, which are intermediate states in the process of mitochondrial fission.

scholarly journals The Mitochondrial Carnitine Acyl-carnitine Carrier (SLC25A20): Molecular Mechanisms of Transport, Role in Redox Sensing and Interaction with Drugs

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 521
Author(s):  
Annamaria Tonazzi ◽  
Nicola Giangregorio ◽  
Lara Console ◽  
Ferdinando Palmieri ◽  
Cesare Indiveri
Keyword(s):  
Molecular Mechanisms ◽  
3D Structure ◽  
Liver Mitochondria ◽  
Carbon Chain ◽  
Site Directed Mutagenesis ◽  
Rat Liver Mitochondria ◽  
Large Set ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Inner Membrane ◽  
Chain Acyl

The SLC25A20 transporter, also known as carnitine acyl-carnitine carrier (CAC), catalyzes the transport of short, medium and long carbon chain acyl-carnitines across the mitochondrial inner membrane in exchange for carnitine. The 30-year story of the protein responsible for this function started with its purification from rat liver mitochondria. Even though its 3D structure is not yet available, CAC is one of the most deeply characterized transport proteins of the inner mitochondrial membrane. Other than functional, kinetic and mechanistic data, post-translational modifications regulating the transport activity of CAC have been revealed. CAC interactions with drugs or xenobiotics relevant to human health and toxicology and the response of the carrier function to dietary compounds have been discovered. Exploiting combined approaches of site-directed mutagenesis with chemical targeting and bioinformatics, a large set of data on structure/function relationships have been obtained, giving novel information on the molecular mechanism of the transport catalyzed by this protein.

Electron Microscopic Tomography of Cellular Organelles: Chemical Fixation Vs. Cryo-Substitution of Rat-Liver Mitochondria

1998 ◽  
Vol 4 (S2) ◽  
pp. 430-431
Author(s):  
C.A. Mannella ◽  
K. Buttle ◽  
K. Tessitore ◽  
B.K. Rath ◽  
C. Hsieh ◽  
...  
Keyword(s):  
Rat Liver ◽  
3D Structure ◽  
Design Feature ◽  
Liver Mitochondria ◽  
Rat Liver Mitochondria ◽  
Electron Microscopic ◽  
Inner Membrane ◽  
Low Contrast ◽  
Mitochondrial Inner Membrane ◽  
Cellular Organelles

Electron microscopic tomography is proving to be a valuable tool for investigating the 3D structure and organization of cellular organelles. Important progress is being made in the application of the technique to frozen-hydrated material, but it is likely that success with thick specimens will be limited by the low contrast and beam sensitivity of naked biological material. Thus, optimizing procedures for fixing, embedding, staining, and selectively labelling cells for 3D electron microscopy remains a priority.Tomography of chemically fixed and plastic-embedded rat-liver tissue and isolated mitochondria has shown that the cristae (the invaginations of the mitochondrial inner membrane) are pleiomorphic and connected to each other and to the surface of the inner membrane by tubular regions 30-40 nm in diameter. This basic design feature has important implications for the microcompartmentation of ions and molecules within this organelle.

scholarly journals Fatal Disseminated Cercopithecine Herpesvirus 1 (Herpes B) Infection in Cynomolgus Monkeys {Macaca fascicularis)

1997 ◽  
Vol 34 (5) ◽  
pp. 405-414 ◽  
Author(s):  
C. S. Carlson ◽  
M. G. O'Sullivan ◽  
M. J. Jayo ◽  
D. K. Anderson ◽  
E. S. Harber ◽  
...  
Keyword(s):  
Macaca Fascicularis ◽  
Nasal Discharge ◽  
Cynomolgus Monkeys ◽  
Watery Stool ◽  
Type D ◽  
Large Numbers ◽  
High Fatality Rate ◽  
Herpesvirus 1 ◽  
Cercopithecine Herpesvirus ◽  
Disseminated Disease

Two adult female cynomolgus monkeys ( Macaca fascicularis) that had been housed together for 4 months died within 2 weeks of each other after brief illnesses. Monkey No. 1 presented with collapse, watery stool, and hypothermia and died overnight. Monkey No. 2 presented with dyspnea, nasal discharge, leukopenia, and hypoproteinemia and was euthanized after 2 days. Both animals had peritoneal effusions, massive necrosis of pharyngeal, esophageal, and gastric mucosa, and multifocal hepatic and pancreatic necrosis. Monkey No. 2 also had lingual ulcers and locally extensive necrosis of spleen, adrenal glands, and lymph nodes. Large numbers of eosinophilic intranuclear inclusion bodies were present in epithelial and syncytial cells adjoining the necrotic foci in Monkey No. 2 but were absent in Monkey No. 1. Monkey No. 1 seroconverted to cercopithecine herpesvirus 1 (CHV-1, commonly known as herpes B) in the month before death. CHV-1 was isolated from a sample of stomach from Monkey No. 2, and electron microscopy of liver from this animal demonstrated herpesvirus particles within hepatocytes. Both animals were seropositive for simian type D retrovirus, and the virus was cultured from the liver of Monkey No. 2. A diagnosis of disseminated CHV-1 infection was made, possibly occurring secondary to immunosuppression due to infection with simian type D retrovirus. Although a high percentage of cynomolgus monkeys are inapparently infected with CHV-1, disseminated disease is rare. Because infection with CHV-1 in humans is associated with a high fatality rate, familiarity with the lesions of disseminated infection with this virus is important.

Comparison of human and monkey retinal photoreceptor sampling mosaics

1989 ◽  
Vol 3 (3) ◽  
pp. 281-285 ◽  
Author(s):  
Chander N. Samy ◽  
Joy Hirsch
Keyword(s):  
Macaca Fascicularis ◽  
Focal Length ◽  
Primate Species ◽  
Retinal Eccentricity ◽  
Sampling Strategies ◽  
Human Eye ◽  
Rods And Cones ◽  
Retinal Photoreceptor ◽  
Photoreceptor Mosaic ◽  
Human Density

AbstractWe test the hypothesis that the diameters of foveal and near-foveal rods and cones for one well-studied human photoreceptor mosaic and one well-studied monkey photoreceptor mosaic (Macaca fascicularis) a scaled relative to focal length. We conclude that this hypothesis is not supported. Rather than being scali proportionally, the sizes of the rods and cones, respectively, are nearly equivalent for both the human ar monkey resulting in an effectively finer retinal grain for the larger human eye. Furthermore, the human density exceeds the monkey rod density beyond about 1 deg of retinal eccentricity. These results suggest variation across primate species is reflected in retinal sampling strategies.

scholarly journals The Mitochondrial Inner Membrane Protein Mitofilin Controls Cristae Morphology

2005 ◽  
Vol 16 (3) ◽  
pp. 1543-1554 ◽  
Author(s):  
George B. John ◽  
Yonglei Shang ◽  
Li Li ◽  
Christian Renken ◽  
Carmen A. Mannella ◽  
...  
Keyword(s):  
Mitochondrial Function ◽  
Metabolic Flux ◽  
Cellular Proliferation ◽  
Mitochondrial Fission ◽  
Mitochondrial Protein ◽  
Electron Microscopic ◽  
Inner Membrane ◽  
Ultrastructural Studies ◽  
Mitochondrial Inner Membrane ◽  
Inner Membrane Protein

Mitochondria are complex organelles with a highly dynamic distribution and internal organization. Here, we demonstrate that mitofilin, a previously identified mitochondrial protein of unknown function, controls mitochondrial cristae morphology. Mitofilin is enriched in the narrow space between the inner boundary and the outer membranes, where it forms a homotypic interaction and assembles into a large multimeric protein complex. Down-regulation of mitofilin in HeLa cells by using specific small interfering RNA lead to decreased cellular proliferation and increased apoptosis, suggesting abnormal mitochondrial function. Although gross mitochondrial fission and fusion seemed normal, ultrastructural studies revealed disorganized mitochondrial inner membrane. Inner membranes failed to form tubular or vesicular cristae and showed as closely packed stacks of membrane sheets that fused intermittently, resulting in a complex maze of membranous network. Electron microscopic tomography estimated a substantial increase in inner:outer membrane ratio, whereas no cristae junctions were detected. In addition, mitochondria subsequently exhibited increased reactive oxygen species production and membrane potential. Although metabolic flux increased due to mitofilin deficiency, mitochondrial oxidative phosphorylation was not increased accordingly. We propose that mitofilin is a critical organizer of the mitochondrial cristae morphology and thus indispensable for normal mitochondrial function.

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