scholarly journals Meeting report from the Mitochondrial Medicine Southeast Regional Symposium — understanding mitochondrial disease and mitochondrial dysfunction: Opportunities and impacts in the clinic and laboratory

2017 ◽  
Vol 2 (3-4) ◽  
pp. 195-214
Author(s):  
Amy Stone ◽  
Phillip Yeske ◽  
Laura Stanley
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Meeting Report ◽  
Mitochondrial Medicine

scholarly journals Imaging mass cytometry reveals generalised deficiency in OXPHOS complexes in Parkinson’s disease

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Chun Chen ◽  
David McDonald ◽  
Alasdair Blain ◽  
Ashwin Sachdeva ◽  
Laura Bone ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Dopaminergic Neurons ◽  
Neuronal Response ◽  
Proteomic Profiling ◽  
Mass Cytometry ◽  
And Control

AbstractHere we report the application of a mass spectrometry-based technology, imaging mass cytometry, to perform in-depth proteomic profiling of mitochondrial complexes in single neurons, using metal-conjugated antibodies to label post-mortem human midbrain sections. Mitochondrial dysfunction, particularly deficiency in complex I has previously been associated with the degeneration of dopaminergic neurons in Parkinson’s disease. To further our understanding of the nature of this dysfunction, and to identify Parkinson’s disease specific changes, we validated a panel of antibodies targeting subunits of all five mitochondrial oxidative phosphorylation complexes in dopaminergic neurons from Parkinson’s disease, mitochondrial disease, and control cases. Detailed analysis of the expression profile of these proteins, highlighted heterogeneity between individuals. There is a widespread decrease in expression of all complexes in Parkinson’s neurons, although more severe in mitochondrial disease neurons, however, the combination of affected complexes varies between the two groups. We also provide evidence of a potential neuronal response to mitochondrial dysfunction through a compensatory increase in mitochondrial mass. This study highlights the use of imaging mass cytometry in the assessment and analysis of expression of oxidative phosphorylation proteins, revealing the complexity of deficiencies of these proteins within individual neurons which may contribute to and drive neurodegeneration in Parkinson’s disease.

scholarly journals Epilepsy in Mitochondrial Diseases—Current State of Knowledge on Aetiology and Treatment

Children ◽  
2021 ◽  
Vol 8 (7) ◽  
pp. 532
Author(s):  
Dorota Wesół-Kucharska ◽  
Dariusz Rokicki ◽  
Aleksandra Jezela-Stanek
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Clinical Picture ◽  
Poor Prognosis ◽  
Treatment Options ◽  
Mitochondrial Diseases ◽  
Energy Deficit ◽  
Atp Production ◽  
Current State

Mitochondrial diseases are a heterogeneous group of diseases resulting from energy deficit and reduced adenosine triphosphate (ATP) production due to impaired oxidative phosphorylation. The manifestation of mitochondrial disease is usually multi-organ. Epilepsy is one of the most common manifestations of diseases resulting from mitochondrial dysfunction, especially in children. The onset of epilepsy is associated with poor prognosis, while its treatment is very challenging, which further adversely affects the course of these disorders. Fortunately, our knowledge of mitochondrial diseases is still growing, which gives hope for patients to improve their condition in the future. The paper presents the pathophysiology, clinical picture and treatment options for epilepsy in patients with mitochondrial disease.

scholarly journals Skeletal Phenotypes Due to Abnormalities in Mitochondrial Protein Homeostasis and Import

2020 ◽  
Vol 21 (21) ◽  
pp. 8327
Author(s):  
Tian Zhao ◽  
Caitlin Goedhart ◽  
Gerald Pfeffer ◽  
Steven C Greenway ◽  
Matthew Lines ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Protein Import ◽  
Mitochondrial Protein ◽  
Membrane Lipid ◽  
Disease Genes ◽  
Protein Homeostasis ◽  
Inner Mitochondrial Membrane ◽  
Mitochondrial Functions ◽  
Insight Into

Mitochondrial disease represents a collection of rare genetic disorders caused by mitochondrial dysfunction. These disorders can be quite complex and heterogeneous, and it is recognized that mitochondrial disease can affect any tissue at any age. The reasons for this variability are not well understood. In this review, we develop and expand a subset of mitochondrial diseases including predominantly skeletal phenotypes. Understanding how impairment ofdiverse mitochondrial functions leads to a skeletal phenotype will help diagnose and treat patients with mitochondrial disease and provide additional insight into the growing list of human pathologies associated with mitochondrial dysfunction. The underlying disease genes encode factors involved in various aspects of mitochondrial protein homeostasis, including proteases and chaperones, mitochondrial protein import machinery, mediators of inner mitochondrial membrane lipid homeostasis, and aminoacylation of mitochondrial tRNAs required for translation. We further discuss a complex of frequently associated phenotypes (short stature, cataracts, and cardiomyopathy) potentially explained by alterations to steroidogenesis, a process regulated by mitochondria. Together, these observations provide novel insight into the consequences of impaired mitochondrial protein homeostasis.

scholarly journals Anesthesia outside the Operating Room in a Patient with Mitochondrial Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-3
Author(s):  
Alejandra Fadrique-Fuentes ◽  
Beatriz Martínez-Rafael ◽  
Rodrigo Poves-Álvarez ◽  
Estefanía Gómez-Pesquera
Keyword(s):  
Mitochondrial Dysfunction ◽  
Operating Room ◽  
Mitochondrial Disease ◽  
Genetic Disorders ◽  
Metabolic Balance ◽  
Anesthetic Agents ◽  
Wide Range

Mitochondrial dysfunction comprehends a wide range of genetic disorders. These patients’ precarious metabolic balance makes its management difficult. Furthermore, the same systems affected by mitochondrial disease can be altered by many of the frequently used anesthetic agents. Each patient has to be evaluated individually according to their comorbidities and anesthetic requirements.

Relapsing remitting multiple sclerosis in progressive external ophthalmoplegia: A report of two cases

2018 ◽  
Vol 25 (6) ◽  
pp. 879-882 ◽  
Author(s):  
Kevin R Patel ◽  
Amel Karaa ◽  
Farrah J Mateen
Keyword(s):  
Multiple Sclerosis ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Progressive External Ophthalmoplegia ◽  
Genetic Mutations ◽  
Mcdonald Criteria ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Relapsing Remitting Multiple Sclerosis

Evidence from genetic and pathologic studies suggests that mitochondrial dysfunction occurs in multiple sclerosis (MS). Furthermore, cases of MS have been reported in patients with mitochondrial disease. The phenotypic range of mitochondrial illness associating with MS is not yet well defined. In this report, we highlight two cases of patients with confirmed genetic mutations responsible for progressive external ophthalmoplegia who independently meet McDonald criteria for MS. Better characterization of the range of mitochondrial disease associated with MS may improve our understanding of MS disease pathophysiology.

scholarly journals Generation of somatic mitochondrial DNA-replaced cells for mitochondrial dysfunction treatment

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hideki Maeda ◽  
Daisuke Kami ◽  
Ryotaro Maeda ◽  
Akira Shikuma ◽  
Satoshi Gojo
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Respiratory Function ◽  
Disease Patient ◽  
Mitochondrial Diseases ◽  
Wild Type ◽  
Mutant Genotype ◽  
Isolated Mitochondria ◽  
Wide Range

AbstractMitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed. Mitochondrial disease patient-derived fibroblasts regained respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. Mitochondrial DNA-replaced cells could be a resource for transplantation to treat maternal inherited mitochondrial diseases.

scholarly journals Mitochondrial DNA Density Homeostasis Accounts for the Threshold Effect in Human Mitochondrial Disease

2016 ◽  
Author(s):  
Juvid Aryaman ◽  
Iain G. Johnston ◽  
Nick S. Jones
Keyword(s):  
Mathematical Model ◽  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Cell Volume ◽  
Mitochondrial Disease ◽  
Large Scale ◽  
Threshold Effect ◽  
Progressive Increase ◽  
Theoretical Understanding ◽  
Demand Reduction

AbstractMitochondrial dysfunction is involved in a wide array of devastating diseases but the heterogeneity and complexity of these diseases’ symptoms challenges theoretical understanding of their causation. With the explosion of -omics data, we have the unprecedented ability to gain deep understanding of the biochemical mechanisms of mitochondrial dysfunction. However, there is also a need to make such datasets interpretable, and quantitative modelling allows us to translate such datasets into intuition and suggest rational biomedical treatments. Working towards this interdisciplinary goal, we use a recently published large-scale dataset, and develop a mathematical model of progressive increase in mutant load of the MELAS 3243A>G mtDNA mutation to develop a descriptive and predictive biophysical model. The experimentally observed behaviour is surprisingly rich, but we find that a simple, biophysically-motivated model intuitively accounts for this heterogeneity and yields a wealth of biological predictions. Our findings suggest that cells attempt to maintain wild-type mtDNA density through cell volume reduction, and thus energy demand reduction, until a minimum cell volume is reached. Thereafter, cells toggle from demand reduction to supply increase, upregulating energy production pathways. Our analysis provides further evidence for the physiological significance of mtDNA density, and emphasizes the need for performing single-cell volume measurements jointly with mtDNA quantification. We propose novel experiments to verify the hypotheses made here, to further develop our understanding of the threshold effect, and connect with rational choices for mtDNA disease therapies.Author SummaryMitochondria are organelles which produce the major energy currency of the cell: ATP. Mitochondrial dysfunction is associated with a multitude of devastating diseases, from Parkinson’s disease to cancer. Large volumes of data related to these diseases are being produced, but translation of these data into rational biomedical treatment is challenged by a lack of theoretical understanding. We develop a mathematical model of progressive increase of mutant load in mitochondrial DNA, for the mutation associated with MELAS (the most common mitochondrial disease), to address this. We predict that cells attempt to maintain the ratio of healthy mtDNA to cell volume by reducing their cell volume until they reach a minimum cell volume. As mutant load continues to increase, cells switch strategy by increasing their energy supply pathways. Our work accounts for large-scale experimental data and makes testable predictions about mitochondrial dysfunction. It also provides support for increasing mitochondrial content, as well as reduction in dependence upon mitochondrial metabolism via the ketogenic diet, as relevant treatments for mitochondrial disease.

scholarly journals Generation of Somatic Mitochondrial DNA-Replaced Cells for Mitochondrial Dysfunction Treatment

2020 ◽  
Author(s):  
Hideki Maeda ◽  
Daisuke Kami ◽  
Ryotaro Maeda ◽  
Akira Shikuma ◽  
Satoshi Gojo
Keyword(s):  
Mitochondrial Dna ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Disease ◽  
Pluripotent Stem Cells ◽  
Disease Patient ◽  
Mitochondrial Diseases ◽  
Wild Type ◽  
Mutant Genotype ◽  
Wide Range

AbstractMitochondrial diseases currently have no cure regardless of whether the cause is a nuclear or mitochondrial genome mutation. Mitochondrial dysfunction notably affects a wide range of disorders in aged individuals, including neurodegenerative diseases, cancers, and even senescence. Here, we present a procedure to generate mitochondrial DNA-replaced somatic cells with a combination of a temporal reduction in endogenous mitochondrial DNA and coincubation with exogeneous isolated mitochondria. Heteroplasmy in mitochondrial disease patient-derived fibroblasts in which the mutant genotype was dominant over the wild-type genotype was reversed over the long term, even inducing the production of pluripotent stem cells from the mitochondrial DNA-replaced cells to maintain the genotype without a reversion to the original. Both mitochondrial disease patient-derived and aged fibroblasts could regain respiratory function and showed lifespan extension. Mitochondrial membranous components were utilized as a vehicle to deliver the genetic materials into endogenous mitochondria-like horizontal genetic transfer in prokaryotes. The mitochondrial DNA-replaced cells could be a resource for transplantation to treat not only mitochondrial diseases, but also senescence-related diseases.

scholarly journals Patient Care Standards for Primary Mitochondrial Disease in Australia. An Australian adaptation of the Mitochondrial Medicine Society recommendations

2021 ◽  
Author(s):  
Carolyn M. Sue ◽  
Shanti Balasubramaniam ◽  
Drago Bratkovic ◽  
Catherine Bonifant ◽  
John Christodoulou ◽  
...  
Keyword(s):  
Patient Care ◽  
Mitochondrial Disease ◽  
Mitochondrial Medicine
Sign in / Sign up

Export Citation Format

Share Document