scholarly journals The genetics of mitochondrial disease: dissecting mitochondrial pathology using multi‐omic pipelines

2021 ◽  
Author(s):  
Charlotte L. Alston ◽  
Sarah L. Stenton ◽  
Gavin Hudson ◽  
Holger Prokisch ◽  
Robert W. Taylor
Keyword(s):  
Mitochondrial Disease ◽  
Mitochondrial Pathology

scholarly journals [11C]PK11195-PET Brain Imaging of the Mitochondrial Translocator Protein in Mitochondrial Disease

Neurology ◽  
2021 ◽  
pp. 10.1212/WNL.0000000000012033
Author(s):  
Jelle van den Ameele ◽  
Young Hong ◽  
Roido Manavaki ◽  
Antonina Kouli ◽  
Heather Biggs ◽  
...  
Keyword(s):  
Brain Imaging ◽  
Mitochondrial Disease ◽  
Structural Changes ◽  
Clinical Severity ◽  
Translocator Protein ◽  
Mitochondrial Outer Membrane ◽  
Class Iii ◽  
Mitochondrial Pathology ◽  
Mr Brain

ObjectiveTo explore the possibilities of radioligands against the mitochondrial outer membrane protein TSPO as biomarkers for mitochondrial disease, we performed PET (PET)-MR brain imaging with [11C]PK11195 in 14 patients with genetically confirmed mitochondrial disease and 33 matched controls.MethodsA case-control study of PET-MR imaging with the TSPO radioligand [11C]PK11195.ResultsForty-six percent of symptomatic patients had volumes of abnormal radiotracer binding greater than the 95th percentile in controls. [11C]PK11195 binding was generally greater in grey matter and significantly decreased in white matter. This was most striking in patients with nuclear TYMP or mitochondrial m.3243A>G MT-TL1 mutations, in keeping with differences in mitochondrial density seen post mortem. Some regional binding patterns corresponded to clinical presentation and underlying mutation, even in the absence of structural changes on MRI. This was most obvious for the cerebellum, where patients with ataxia had decreased binding in the cerebellar cortex, but not necessarily volume loss. Overall, there was a positive correlation between aberrant [11C]PK11195 binding and clinical severity.ConclusionThese findings endorse the use of PET imaging with TSPO radioligands as a non-invasive in vivo biomarker of mitochondrial pathology.Classification of evidenceThis study provides Class III evidence that PET-MR brain imaging with TSPO radioligands identifies mitochondrial pathology.

Mitochondrial Pathology in Osteoarthritic Chondrocytes

2014 ◽  
Vol 15 (7) ◽  
pp. 710-719 ◽  
Author(s):  
Longhuo Wu ◽  
Haiqing Liu ◽  
Linfu Li ◽  
Hai Liu ◽  
Qilai Cheng ◽  
...  
Keyword(s):  
Osteoarthritic Chondrocytes ◽  
Mitochondrial Pathology

scholarly journals Targeting ferroptosis: A novel therapeutic strategy for the treatment of mitochondrial disease-related epilepsy

PLoS ONE ◽  
2019 ◽  
Vol 14 (3) ◽  
pp. e0214250 ◽  
Author(s):  
Amanda H. Kahn-Kirby ◽  
Akiko Amagata ◽  
Celine I. Maeder ◽  
Janet J. Mei ◽  
Steve Sideris ◽  
...  
Keyword(s):  
Mitochondrial Disease ◽  
Therapeutic Strategy ◽  
Novel Therapeutic

scholarly journals General anesthesia with remimazolam in a patient with mitochondrial encephalomyopathy: a case report

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuji Suzuki ◽  
Matsuyuki Doi ◽  
Yoshiki Nakajima
Keyword(s):  
Lactic Acidosis ◽  
General Anesthesia ◽  
Mitochondrial Disease ◽  
Muscle Relaxation ◽  
Anesthetic Management ◽  
Perioperative Period ◽  
Mitochondrial Encephalomyopathy ◽  
Anesthesia Induction ◽  
General Anesthetic ◽  
Anesthetic Agents

Abstract Background Systemic anesthetic management of patients with mitochondrial disease requires careful preoperative preparation to administer adequate anesthesia and address potential disease-related complications. The appropriate general anesthetic agents to use in these patients remain controversial. Case presentation A 54-year-old woman (height, 145 cm; weight, 43 kg) diagnosed with mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes underwent elective cochlear implantation. Infusions of intravenous remimazolam and remifentanil guided by patient state index monitoring were used for anesthesia induction and maintenance. Neither lactic acidosis nor prolonged muscle relaxation occurred in the perioperative period. At the end of surgery, flumazenil was administered to antagonize sedation, which rapidly resulted in consciousness. Conclusions Remimazolam administration and reversal with flumazenil were successfully used for general anesthesia in a patient with mitochondrial disease.

scholarly journals Risk of cardiac manifestations in adult mitochondrial disease caused by nuclear genetic defects

Open Heart ◽  
2021 ◽  
Vol 8 (1) ◽  
pp. e001510
Author(s):  
Albert Zishen Lim ◽  
Daniel M Jones ◽  
Matthew G D Bates ◽  
Andrew M Schaefer ◽  
John O'Sullivan ◽  
...  
Keyword(s):  
Mitochondrial Disease ◽  
Nuclear Dna ◽  
Laboratory Data ◽  
Nuclear Genome ◽  
Nuclear Gene ◽  
Left Ventricular ◽  
Adult Patients ◽  
Limited Information ◽  
Cardiac Abnormalities ◽  
Cardiac Manifestations

ObjectiveRegular cardiac surveillance is advocated for patients with primary mitochondrial DNA disease. However, there is limited information to guide clinical practice in mitochondrial conditions caused by nuclear DNA defects. We sought to determine the frequency and spectrum of cardiac abnormalities identified in adult mitochondrial disease originated from the nuclear genome.MethodsAdult patients with a genetically confirmed mitochondrial disease were identified and followed up at the national clinical service for mitochondrial disease in Newcastle upon Tyne, UK (January 2009 to December 2018). Case notes, molecular genetics reports, laboratory data and cardiac investigations, including serial electrocardiograms and echocardiograms, were reviewed.ResultsIn this cohort-based observational study, we included 146 adult patients (92 women) (mean age 53.6±18.7 years, 95% CI 50.6 to 56.7) with a mean follow-up duration of 7.9±5.1 years (95% CI 7.0 to 8.8). Eleven different nuclear genotypes were identified: TWNK, POLG, RRM2B, OPA1, GFER, YARS2, TYMP, ETFDH, SDHA, TRIT1 and AGK. Cardiac abnormalities were detected in 14 patients (9.6%). Seven of these patients (4.8%) had early-onset cardiac manifestations: hypertrophic cardiomyopathy required cardiac transplantation (AGK; n=2/2), left ventricular (LV) hypertrophy and bifascicular heart block (GFER; n=2/3) and mild LV dysfunction (GFER; n=1/3, YARS2; n=1/2, TWNK; n=1/41). The remaining seven patients had acquired heart disease most likely related to conventional cardiovascular risk factors and presented later in life (14.6±12.8 vs 55.1±8.9 years, p<0.0001).ConclusionsOur findings demonstrate that the risk of cardiac involvement is genotype specific, suggesting that routine cardiac screening is not indicated for most adult patients with nuclear gene-related mitochondrial disease.

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.

Experiences of adults living and coping with primary mitochondrial disease

2021 ◽  
Vol 132 ◽  
pp. S210
Author(s):  
Kathleen Valverde ◽  
Elizabeth McCormick ◽  
Marni Falk
Keyword(s):  
Mitochondrial Disease ◽  
And Coping
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