Mitochondrial Myopathy With a Defect in Mitochondrial Protein Transport

Last update 01 Nov 2024

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Synonyms

MITOCHONDRIAL MYOPATHY WITH A DEFECT IN MITOCHONDRIAL-PROTEIN TRANSPORT, Mitochondrial Myopathy with a Defect in Mitochondrial Protein Transport, 线粒体蛋白转运缺陷的线粒体肌病

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100 Clinical Results associated with Mitochondrial Myopathy With a Defect in Mitochondrial Protein Transport

100 Translational Medicine associated with Mitochondrial Myopathy With a Defect in Mitochondrial Protein Transport

0 Patents (Medical) associated with Mitochondrial Myopathy With a Defect in Mitochondrial Protein Transport

Literatures (Medical) associated with Mitochondrial Myopathy With a Defect in Mitochondrial Protein Transport

01 Jul 2012·Journal of Neuroscience MethodsQ4 · MEDICINE

A microdevice platform for visualizing mitochondrial transport in aligned dopaminergic axons

Q4 · MEDICINE

Article

Author: Shelly E. Sakiyama-Elbert ; Xi Lu ; Karen L. O’Malley ; Jeong S. Kim-Han

Experimental evidence points to the importance of mitochondrial transport defects in contributing to major neurodegenerative diseases, such as Parkinson's disease (PD). Studies of mitochondrial transport along single axons are difficult with traditional dissociated culture systems and the fragility of the midbrain dopaminergic cultures precludes their survival in previously developed microfluidic devices with an enclosed architecture. Using soft lithography, we generated a microdevice from polydimethylsiloxane (PDMS) for the purpose of studying the transport of mitochondria along single dopaminergic axons. The device comprises two large open culture chambers connected by a parallel array of microchannels that achieves fluidic separation of axons from the soma and allows the tracking of mitochondrial movement along oriented axons. Dopaminergic neurons from midbrain cultures were successfully cultured within the microdevices for up to 4 weeks and extended their axons across the microchannels. Axonal mitochondria within the microchannels were labeled by transduction with a mitochondrial-targeted DsRed2 lentiviral vector or with the mitochondria-specific dye, Mitotracker Deep Red and were visually tracked with conventional confocal microscopy. The methodology and device that we have described here will allow further study of the role of mitochondrial transport defects play in major neurodegenerative diseases.

Translational Neurodegeneration

The use of fibroblasts as a valuable strategy for studying mitochondrial impairment in neurological disorders

Review

Author: Olesen, Margrethe A ; Villavicencio-Tejo, Francisca ; Quintanilla, Rodrigo A

AbstractNeurological disorders (NDs) are characterized by progressive neuronal dysfunction leading to synaptic failure, cognitive impairment, and motor injury. Among these diseases, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS) have raised a significant research interest. These disorders present common neuropathological signs, including neuronal dysfunction, protein accumulation, oxidative damage, and mitochondrial abnormalities. In this context, mitochondrial impairment is characterized by a deficiency in ATP production, excessive production of reactive oxygen species, calcium dysregulation, mitochondrial transport failure, and mitochondrial dynamics deficiencies. These defects in mitochondrial health could compromise the synaptic process, leading to early cognitive dysfunction observed in these NDs. Interestingly, skin fibroblasts from AD, PD, HD, and ALS patients have been suggested as a useful strategy to investigate and detect early mitochondrial abnormalities in these NDs. In this context, fibroblasts are considered a viable model for studying neurodegenerative changes due to their metabolic and biochemical relationships with neurons. Also, studies of our group and others have shown impairment of mitochondrial bioenergetics in fibroblasts from patients diagnosed with sporadic and genetic forms of AD, PD, HD, and ALS. Interestingly, these mitochondrial abnormalities have been observed in the brain tissues of patients suffering from the same pathologies. Therefore, fibroblasts represent a novel strategy to study the genesis and progression of mitochondrial dysfunction in AD, PD, HD, and ALS. This review discusses recent evidence that proposes fibroblasts as a potential target to study mitochondrial bioenergetics impairment in neurological disorders and consequently to search for new biomarkers of neurodegeneration.

BiomoleculesQ3 · BIOLOGY

Ubiquitination of Intramitochondrial Proteins: Implications for Metabolic Adaptability

Q3 · BIOLOGY

ReviewOA

Author: Ram, Jonathan ; Glickman, Michael H ; Sulkshane, Prasad

Mitochondria are constantly subjected to stressful conditions due to their unique physiology and organization. The resulting damage leads to mitochondrial dysfunction, which underlies many pathophysiological conditions. Hence, constant surveillance is required to closely monitor mitochondrial health for sound maintenance of cellular metabolism and thus, for viability. In addition to internal mitochondrial chaperones and proteases, mitochondrial health is also governed by host cell protein quality control systems. The ubiquitin-proteasome system (UPS) and autophagy constitute the main pathways for removal of damaged or superfluous proteins in the cytosol, nucleus, and from certain organelles such as the Endoplasmic Reticulum (ER) and mitochondria. Although stress-induced ubiquitin-dependent degradation of mitochondrial outer membrane proteins has been widely studied, mechanisms of intramitochondrial protein ubiquitination has remained largely elusive due to the predominantly cytosolic nature of UPS components, separated from internal mitochondrial proteins by a double membrane. However, recent research has illuminated examples of intramitochondrial protein ubiquitination pathways and highlighted their importance under basal and stressful conditions. Owing to the dependence of mitochondria on the error-prone process of protein import from the cytosol, it is imperative that the cell eliminate any accumulated proteins in the event of mitochondrial protein import deficiency. Apparently, a significant portion of this activity involves ubiquitination in one way or another. In the present review article, following a brief introduction to mitochondrial protein quality control mechanisms, we discuss our recent understanding of intramitochondrial protein ubiquitination, its importance for basal function of mitochondria, metabolic implications, and possible therapeutic applications.

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