scholarly journals Mitochondrial Complex I Deficiency among Egyptian Pediatric Patients with Steroid-Resistant Nephrotic Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Doaa M. Abdou ◽  
AbdelAal Mohamed ◽  
Mohamed Abdulhay ◽  
Sara El Khateeb
Keyword(s):  
Nephrotic Syndrome ◽  
Complex I ◽  
Pediatric Patients ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Glomerular Diseases ◽  
Steroid Resistant ◽  
Complex I Deficiency ◽  
Renal Biopsies ◽  
Complex I Activity

Background and objectives. Nephrotic Syndrome (NS) is one of the most common glomerular diseases among children. Up to 20% of patients are steroid resistant (SRNS) representing a challenging subset at high risk of developing end-stage renal disease. Renal manifestations of mitochondrial diseases (MIDs) include nephrotic syndrome, renal insufficiency, nephrolithiasis, Bartter-like syndrome, focal segmental glomerulosclerosis, and nephrocalcinosis. The objective of the current study is to measure the activity of mitochondrial complex I in renal biopsies obtained from pediatric patients diagnosed with SRNS compared to steroid-sensitive nephrotic syndrome (SSNS) patients in order to elucidate its role in pathogenesis and the prognosis for further genetic work. Subjects and Method. Renal biopsies of 120 patients diagnosed with nephrotic syndrome based on clinical and laboratory findings, divided into two groups, SRNS (60 patients) and SSNS (60 patients). Pathological study and spectrophotometric measurement of mitochondrial complex I in renal biopsy and muscle homogenates were performed for both groups. Results. Positive consanguinity was a remarkable finding in 44 patients among the SRNS group (73%), compared with 33 patients among the SSNS group (55%). Complex I activity was significantly lower in the SRNS group (0.2657 ± 0.1831 nmol/ml/min), than in the SSNS group (0.4773 ± 0.1290 nmol/ml/min) ( p < 0.001 ). There was a significant positive correlation between complex I activity and the heaviness of proteinuria among the SRNS group (r 0.344, p < 0.001 ). There were statistically significant differences in serum C3 and C4 levels between both groups ( p < 0.001 , 0.053, respectively). Conclusion. Mitochondrial complex I deficiency in patients who have a nephrotic syndrome complaint may play a role in their responsiveness to steroid therapy and the development of SRNS and even the prognosis of their illness.

Abstract 224: Mitochondrial Complex I Deficiency Promotes Oxidative Stress During Ischemia Reperfusion Of Cardiac Myocytes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Guohua Gong ◽  
Georgios Karamanlidis ◽  
Chi Fung Lee ◽  
Rong Tian ◽  
Wang Wang
Keyword(s):  
Oxidative Stress ◽  
Cardiac Myocytes ◽  
Complex I ◽  
Ischemia Reperfusion ◽  
Mitochondrial Complex I ◽  
Ros Production ◽  
Mitochondrial Complex ◽  
Complex I Deficiency ◽  
Mitochondrial Ros ◽  
Complex I Activity

Normal cardiac function relies on highly coordinated intracellular events, such as calcium cycling and contraction, with adequate mitochondrial energy metabolism. However, mitochondrial respiration unavoidably produces reactive oxygen species (ROS) as electrons leak from the electron transport chain (ETC). Complex I of the ETC is believed to be the major site for ROS generation in the mitochondria. However, suppression of Complex I activity by chemical inhibitors leads to oxidative cell damage. In this study, we used a genetic model of Complex I deficiency, in which a key component of Complex I, Ndufs4, was deleted in the heart, to determine the causal role of Complex I in ischemia-reperfusion-induced oxidative stress in adult cardiac myocytes. Germline deletion of Ndufs4 in the heart (Ndufs4H-/-) leads to a ~75% decline of Complex I activity in cardiac mitochondria without obvious disease phenotype in the mice. As predicted, the mitochondrial respiration-coupled superoxide production events, superoxide flashes, were significantly decreased at baseline in the Ndufs4H-/- myocytes. Respiration substrate (pyruvate, 20 mM) failed to stimulate mitochondrial superoxide flash production in Ndufs4H-/- myocytes. This is accompanied by the slightly decreased steady state intracellular and mitochondrial ROS levels determined by the targeted H2O2 indicator, Hyper. The intracellular redox homeostasis is also tilted toward more reduced state, since the NADH/NAD ratio increased 67%. Surprisingly, ischemia reperfusion mimetic treatment of the myocytes caused dramatic increase in mitochondrial ROS production in Ndufs4H-/- groups, which contributed to the elevated overall cellular oxidative status. Overexpression of catalase in the mitochondria prevented these effects. Mechanistically, increased reducing equivalent (NADH) contributed to the dramatic ROS production during ischemia and reperfusion in Ndufs4H-/- myocytes. In summary, mitochondrial Complex I plays a critical role in controlling mitochondrial and cytosolic ROS homeostasis under normal conditions, and compromised Complex I function leads to accumulation of electron donors that paradoxically promote ROS production during ischemia reperfusion.

CFM6 is an Essential CRM Protein Required for the Splicing of nad5 Transcript in Arabidopsis Mitochondria

2021 ◽  
Author(s):  
Wei-Chih Lin ◽  
Ya-Huei Chen ◽  
Shin-Yuan Gu ◽  
Hwei-Ling Shen ◽  
Kai-Chau Huang ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
High Accumulation ◽  
Stunted Growth ◽  
Growth Defects ◽  
Group I ◽  
Or Genes ◽  
Complex I Activity ◽  
Intron 4

Abstract Plant CRM domain-containing proteins are capable of binding RNA to facilitate the splicing of group I or II introns in chloroplasts, but their functions in mitochondria are less clear. In the present study, Arabidopsis thaliana CFM6, a protein with a single CRM domain, was expressed in most plant tissues, particularly in flower tissues, and restricted to mitochondria. Mutation of CFM6 causes severe growth defects, including stunted growth, curled leaves, delayed embryogenesis, and pollen development. CFM6 functions specifically in the splicing of group II intron 4 of nad5, which encodes a subunit of mitochondrial complex I, as evidenced by the loss of nad5 intron 4 splicing and high accumulation of its pretranscripts in cfm6 mutants. The phenotypic and splicing defects of cfm6 were rescued in transgenic plants overexpressing 35S::CFM6-YFP. Splicing failure in cfm6 also led to the loss of complex I activity and to its improper assembly. Moreover, dysfunction of complex I induced the expression of proteins or genes involved in alternative respiratory pathways in cfm6. Collectively, CFM6, a previously uncharacterized CRM domain-containing protein, is specifically involved in the cis-splicing of nad5 intron 4 and plays a pivotal role in mitochondrial complex I biogenesis and normal plant growth.

scholarly journals Corrigendum: Hepatic S6K1 Partially Regulates Lifespan of Mice with Mitochondrial Complex I Deficiency

2017 ◽  
Vol 8 ◽  
Author(s):  
Takashi K. Ito ◽  
Chenhao Lu ◽  
Jacob Khan ◽  
Quy Nguyen ◽  
Heather Z. Huang ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Complex I Deficiency

Familial Mitochondrial Complex I Deficiency with an Abnormal Mitochondrial Encoded Protein

1989 ◽  
Vol 12 (S2) ◽  
pp. 355-357 ◽  
Author(s):  
P. G. Barth ◽  
P. A. Bolhuis ◽  
F. A. Wijburg ◽  
K. M. C. Sinjorgo ◽  
W. Ruitenbeek ◽  
...  
Keyword(s):  
Complex I ◽  
Mitochondrial Complex I ◽  
Mitochondrial Complex ◽  
Complex I Deficiency
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