China
Africa
Explore chapters and articles related to this topic
Clinical Manifestation of Mitochondrial Disorders in Childhood
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Leigh syndrome (Leigh, 1951) itself has two different meanings. The first represents the radiological or pathological findings of focal bilaterally symmetrical lesions, especially in the thalamus and brainstem regions. The other broadens this meaning to the clinical unit also known as subacute necrotizing encephalomyelopathy. Genetically, LS is very heterogenous and should be defined in by specific mutation or protein deficit where possible, as some particular may specifically differ in their clinical manifestation (e.g., SURF1 or pyruvate-dehydrogenase complex deficiency). In general, LS may be caused by deficits of respiratory chain complex subunits (complex I, II, IV, and V) and their cofactors (e.g., co-enzyme Q10), mutations in nDNA (e.g., SCO2, SURF1), mtDNA encoded tRNA, or the pyruvate dehydrogenase complex (Loeffen et al., 2000; Finsterer, 2008). Mitochondrial respiratory chain complex I (nicotinamide adenine dinucleotide-ubiquinone oxidoreductase) is the largest enzymatic complex of the mitochondrial respiratory chain. Defects in complex I due to nuclear DNA mutations are one of the most frequent casuses of LS. Various mutations in subunits of complex I encoded by nDNA (NDUFV1, NDUFV2, NDUFS1, NDUFS2, NDUFS3, NDUFS4, NDUFS7, and NDUFS8 were reported (Marin et al., 2013).
Gene expression study of mitochondrial complex I in schizophrenia and paranoid personality disorder
Published in The World Journal of Biological Psychiatry, 2018
Arvin Haghighatfard, Sarah Andalib, Mozhdeh Amini Faskhodi, Soha Sadeghi, Amir Hossein Ghaderi, Shadi Moradkhani, Jalal Rostampour, Zeinab Tabrizi, Ali Mahmoodi, Talie Karimi, Zakieh Ghadimi
Gene expression studies of mitochondrial complex I help to clarify the pattern of bioenergetics effects in behaviour and psychiatric disorders. Several studies which considered the gene expression of the largest subunits of mitochondrial complex I presented it as potential peripheral biomarker for SCZ (Taurines et al. 2010; Akarsu et al. 2014). The present study examined gene expression of whole subunits in complex I in two psychiatric disorders for the first time, and detected a pattern of gene expression alterations including up- and down-regulations showing the importance of small subunits as well. This is the first gene expression study in PPD. Shared gene expression patterns of both disorders support the hypothesis of a similarity in pathophysiology of PPD and SCZ. Eighteen candidate genes were detected in SCZ and 11 genes in PPD; all of the candidate genes found in PPD were among the 18 differentially expressed genes found in SCZ and their alteration directions were the same in both disorders. These findings confirmed role of genomic core subunits in SCZ. Down-regulation of NDUFS7 and NDUFS8 along with up-regulation of NDUFS1, NDUFV1 and NDUFV2 were detected in both SCZ and PPD patients. Deregulation of these five subunits from 14 core subunits may cause abnormal structured complex I in neural cells, which leads to abnormal energetic state and altered neural activity. None of the seven mitochondrial genes showed a change in expression, which may reduce the importance of a maternal pattern in the heritance of SCZ and PPD. Over-expression of several supernumerary subunits was detected in SCZ and PPD patients. As oxidative stress is increased in psychiatric disorders, it may relate to the role of supernumerary subunits in protection against oxidative stress. Under-expression of five supernumerary subunits was detected in SCZ. Under-expression of NDUFB11 (which is only under-expressed in supernumerary subunits in PPD patients) was reported in brain tissue samples from SCZ patients (Huang et al. 2014). Also, down-regulation of the NDUFA1 gene was reported in progressive neurodegenerative diseases, including Alzheimer’s disease (Fernandez‐Moreira et al. 2007).
Single-cell analysis reveals immune modulation and metabolic switch in tumor-draining lymph nodes
Published in OncoImmunology, 2020
Yen-Liang Li, Chung-Hsing Chen, Jing-Yi Chen, You-Syuan Lai, Shao-Chun Wang, Shih-Sheng Jiang, Wen-Chun Hung
Based on relatively stringent criteria to remove low-quality cells, a total of 98 FRCs were identified using the expression of marker gene Vim and these cells were classified into 4 subclusers using SC3 Figure 5a. Based on GSVA, 18 hallmark pathways were significantly associated with transcriptional alterations between FRCs in TDLNs and those in naive LNs (q-value < 0.1; Figure 5c). Intriguingly, oxidative phosphorylation (OXPHOS) pathway and peroxisome pathway were among the top 3 significantly upregulated pathways in TDLNs. Several genes involved in OXPHOS were selected and their differential expression (p-value < 0.05) represented by violin plot were shown in Figure 5d. Among them, cytochrome c oxidase subunit 7 C (Cox7c), which catalyzes the electron transfer from reduced cytochrome c to oxygen, is a subunit of complex IV of mitochondrion; NADH dehydrogenase flavoprotein 2 (Ndufv2) is a subunit of complex I that catalyzes the transfer of electrons from NADH to ubiquinone; Ndufa4 functioning as a NADH dehydrogenase with oxidoreductase activity on complex I;52 Ubiquinol-cytochrome c reductase, complex III sub-unit XI (Uqcr11) may function as a binding factor for the iron-sulfur protein in complex III, which is ubiquitous expressed in human cells; Peroxiredoxin-5 (Prdx5) is a peroxidase that can use cytosolic or mitochondrial thioredoxins to reduce alkyl hydroperoxides or peroxynitrite. PRDX5 has been shown to be a cytoprotective antioxidant enzyme that inhibits endogenous or exogenous peroxide accumulation.53 Our data are consistent to previous finding that FRCs in TDLNs immediately downstream of tumors undergo an altered function of FRCs’ mitochondria;54 our analysis further suggested a significantly upregulated OXPHOS pathway activity in FRCs of TDLNs. We also summarized the genes differentially expressed in OXPHOS pathways annotated by KEGG database. Interestingly, among 47 upregulated mitochondrial genes encoding proteins of respiratory chain, 27 genes are from complex I, 1 complex II, 6 complex III, 9 complex IV, and 4 complex V Figure 6a. These observations suggested a massive ATP consumption and consequently possible DNA damage followed by OXPHOS may occur during tumor progression in the TDLNs. To validate the change of OXPHOS pathway, we investigated extracellular oxygen consumption rates (OCR) in FRCs treated with or without the conditioned media of 4T1 mouse breast cancer cells or MMTV-PyMT cancer cells. Significant increase of OCR was found in the FRCs treated with the conditioned media of breast cancer cells Figure 6c.