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Role of Tandem Mass Spectrometry in Diagnosis and Management of Inborn Errors of Metabolism
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Kannan Vaidyanathan, Sandhya Gopalakrishnan
Proteomic studies (2DE-MS/MS) on multiple acyl-CoA dehydrogenase deficiency (MADD) identified differentially expressed proteins associated to binding/folding functions, mitochondrial antioxidant enzymes and proteins associated to apoptotic events. 35 mitochondrial proteins showed significant changes compared to controls reflecting mitochondrial protein plasticity in the disease [71]. 24 salivary auto-antibodies were detected in Sjogren’s syndrome, out of which 4 were validated, anti-transglutaminase, anti-histone, anti-SSA, and anti-SSB. The new biomarkers may be used for early identification of Sjogren’s syndrome [72].
Responses to Muscular Exercise, Heat Shock Proteins as Regulators of Inflammation, and Mitochondrial Quality Control
Published in Peter M. Tiidus, Rebecca E. K. MacPherson, Paul J. LeBlanc, Andrea R. Josse, The Routledge Handbook on Biochemistry of Exercise, 2020
Alex T. Von Schulze, Paige C. Geiger
In addition to their roles in signalling and protein folding/degradation, HSPs facilitate the translocation of precursor proteins into the mitochondria. HSP70 and HSP90 translocate precursor proteins with mitochondrial localization sequences to the outer mitochondrial membrane, transferring them to the translocase receptor TOM70 for mitochondrial import (13, 99). Upon import through the TOM and TIM complexes on the outer and inner mitochondrial membrane, respectively, intramitochondrial HSP70 folds the protein into its native functional form (13). As most mitochondrial proteins are encoded by nuclear deoxyribonucleic acid (DNA) and made in the ER, cytoplasmic transport and mitochondrial import of mitochondrial target proteins are critical for overall mitochondrial health and function. In this way, HSPs are indirectly or directly involved in energy homeostasis.
Introduction to lactic acidemias
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop
Mitochondrial proteins synthesized in the cytosol must be transported into the mitochondria. Defects in the transport proteins could provide another novel mechanism of the pathogenesis of mitochondrial disease. Two of these protein complexes, translocation outer mitochondrial membrane (TOMM) and translocation inner mitochondrial membrane (TIMM), have been extensively studied in yeast in which the genes have been characterized. The human gene encoding an ortholog of TOMM 20 has been identified [24], and the human genome project has made the genes for other orthologs available. A search for abnormalities causing human disease is under way. Among the transporters of the mitochondria is an outer membrane transporter known as voltage-dependent ion channel (VDAC) and also known as mitochondrial porin, because it forms a pore, opening the membrane for anions like phosphate, chloride, and adenine nucleotides at low transmembrane voltage; at high voltage, it forms a channel for cations and uncharged molecules. A deficiency in VDAC has been reported in Western blot studies [25] in a patient with impaired myopathy and impaired oxidation of pyruvate in mitochondria of muscle. Lactate was elevated only mildly after 2 g/kg of glucose.
Passive heat stress induces mitochondrial adaptations in skeletal muscle
Published in International Journal of Hyperthermia, 2023
Erik D. Marchant, W. Bradley Nelson, Robert D. Hyldahl, Jayson R. Gifford, Chad R. Hancock
Aside from the apparent role of HSP72 in activating PGC-1α through AMPK and SIRT1, heat shock proteins play a vital role in the import of nuclear-encoded mitochondrial proteins into the mitochondrial matrix, as well as in helping fold and assemble them into complexes [52]. The mitochondrial proteome is composed of over 1,000 proteins, 99% of which are nuclear encoded, with only 13 being coded for by mitochondrial DNA [80]. Because most mitochondrial proteins are translated outside the mitochondria, specialized import machinery is required to introduce newly synthesized proteins into the mitochondrial matrix. Two primary players in this process are the translocase of the outer membrane (TOM), and the translocase of the inner membrane (TIM) [81]. Interestingly, both cytosolic and mitochondrial heat shock proteins are vital for this translocation process, partially due to their interactions with TIM and TOM [81–83]. Furthermore, once introduced into the mitochondria, heat shock protein 60 is necessary for the proper folding and assembly of the respiratory complexes of the electron transport system [84]. To date, it is unknown if passive heating in humans or animals improves protein import and folding due to increased HSP content or activation in skeletal muscle. However, the vital role of HSPs in mitochondrial protein import and assembly suggests that this is an important area for future research.
Liposome as drug delivery system enhance anticancer activity of iridium (III) complex
Published in Journal of Liposome Research, 2021
Yiying Gu, Lan Bai, Yuanyuan Zhang, Huiwen Zhang, Degang Xing, Li Tian, Yi Zhou, Jing Hao, Yunjun Liu
Normal mitochondrial function requires a harmonious interaction between many key mitochondrial proteins. As a critical protein in mitochondrial electron transport and cellular metabolism, cytochrome c (cyto c) plays a key role in maintaining normal MMP (mitochondrial membrane potential) (Ma et al. 2012). Most of cell stress and pro-apoptotic proteins can act as upstream stimuli to initiate the mitochondrial apoptotic pathway, leading to cyto c release from the mitochondria into the cytoplasm. Hereafter, combining with the apoptotic protease, cyto c will activate factor-1 (Apaf-1) and caspase-9, further to produce apoptosomes to mediate the activation of caspase-9, resulting in down-stream caspases activation and caspase-dependent apoptosis (Hockenbery 2010, Fulda 2013). We monitored the release of cytochrome c, see from Figure S8(A,B) (Supporting information), by monitoring the fluorescence intensity increase dramatically after exposure of HepG2 cells to Ir1Lipo (4.0 μM) for 24 h, indicating that cytochrome c was mainly accumulated in the cytoplasm, whereas Ir1 showed only a weak effect on the release of cytochrome c (again by monitoring fluorescence intensity (much smaller signal)).
An overview of the human brain myelin proteome and differences associated with schizophrenia
Published in The World Journal of Biological Psychiatry, 2021
Daniel Martins-de-Souza, Paul C. Guest, Guilherme Reis-de-Oliveira, Andrea Schmitt, Peter Falkai, Christoph W. Turck
In our study, the enrichment of specific cellular compartments, components and brain structures supports the validity of the isolation procedure, as does the Western blot shown in Figure 1(A). We have identified a number of mitochondrial proteins associated with metabolism and energy functions. Previous studies have suggested that mitochondria appear as a contaminant in purified myelin preparations (Taylor et al. 2004; Roth et al. 2006). Another research group hypothesised that myelin actually acts like a mitochondrion, by generating energy in the form of ATP across its membranes (Ravera et al. 2009). However, this proposal has been refuted by another study which suggested that if the respiratory chain was present in the myelin membranes, ATP synthase would function in reverse (Harris and Attwell 2013). Nevertheless, our finding that the human myelinome is also enriched with proteins associated with classical degenerative brain diseases such as Parkinson’s, Huntington’s and Alzheimer’s disease, is consistent with the importance of myelin in these illnesses and highlights the specific proteins participating in this context.