scholarly journals Effects of Aging on Activities of Mitochondrial Electron Transport Chain Complexes and Oxidative Damage in Rat Heart

2011 ◽  
pp. 281-289 ◽  
Author(s):  
Z. TATARKOVÁ ◽  
S. KUKA ◽  
P. RAČAY ◽  
J. LEHOTSKÝ ◽  
D. DOBROTA ◽  
...  
Keyword(s):  
Electron Transport ◽  
Oxidative Damage ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Thiol Group ◽  
Mitochondrial Electron Transport Chain ◽  
Age Related ◽  
Transport Chain ◽  
Old Rats ◽  
Major Factors

Mitochondrial dysfunction and accumulation of oxidative damage have been implicated to be the major factors of aging. However, data on age-related changes in activities of mitochondrial electron transport chain (ETC) complexes remain controversial and molecular mechanisms responsible for ETC dysfunction are still largely unknown. In this study, we examined the effect of aging on activities of ETC complexes and oxidative damage to proteins and lipids in cardiac mitochondria from adult (6-month-old), old (15-month-old) and senescent (26-month-old) rats. ETC complexes I-IV displayed different extent of inhibition with age. The most significant decline occurred in complex IV activity, whereas complex II activity was unchanged in old rats and was only slightly reduced in senescent rats. Compared to adult, old and senescent rat hearts had significantly higher levels of malondialdehyde, 4-hydroxynonenal (HNE) and dityrosine, while thiol group content was reduced. Despite marked increase in HNE content with age (25 and 76 % for 15- and 26-month-old rats, respectively) Western blot analysis revealed only few HNE-protein adducts. The present study suggests that non-uniform decline in activities of ETC complexes is due, at least in part, to mitochondrial oxidative damage; however, lipid peroxidation products appear to have a limited impact on enzyme functions.

scholarly journals A mitochondrial electron transport chain with atypical subunit composition confers oxygen sensitivity to a mammalian chemoreceptor

2021 ◽  
Author(s):  
Alba Timon-Gomez ◽  
Alexandra L Scharr ◽  
Nicholas Y Wong ◽  
Erwin Ni ◽  
Arijit Roy ◽  
...  
Keyword(s):  
Electron Transport ◽  
Electron Transport Chain ◽  
Molecular Mechanisms ◽  
Gene Knockout ◽  
Oxygen Sensing ◽  
Acute Hypoxia ◽  
Physiological Adaptation ◽  
Mitochondrial Electron Transport Chain ◽  
Glomus Cells ◽  
Transport Chain

The carotid body (CB) is the major chemoreceptor for blood oxygen in the control of ventilation in mammals, contributing to physiological adaptation to high altitude, pregnancy, and exercise, and its hyperactivity is linked to chronic conditions such as sleep-disorder breathing, hypertension, chronic heart failure, airway constriction, and metabolic syndrome. Upon acute hypoxia (PO2=100 mmHg to <80 mmHg), K+ channels on CB glomus cells are inhibited, causing membrane depolarization to trigger Ca+2 influx and neurotransmitter release that stimulates afferent nerves. A longstanding model proposes that the CB senses hypoxia through atypical mitochondrial electron transport chain (ETC) metabolism that is more sensitive to decreases in oxygen than other tissues. This model is supported by observations that ETC inhibition by pharmacology and gene knockout activates CB sensory activity and that smaller decreases in oxygen concentration inhibit ETC activity in CB cells compared to other cells. Determining the composition of atypical ETC subunits in the CB and their specific activities is essential to delineate molecular mechanisms underlying the mitochondrial hypothesis of oxygen sensing. Here, we identify HIGD1C, a novel hypoxia inducible gene domain factor isoform, as an ETC Complex IV (CIV) protein highly and selectively expressed in glomus cells that mediates acute oxygen sensing by the CB. We demonstrate that HIGD1C negatively regulates oxygen consumption by CIV and acts with the hypoxia-induced CIV subunit COX4I2 to enhance the sensitivity of CIV to hypoxia, constituting an important component of mitochondrial oxygen sensing in the CB. Determining how HIGD1C and other atypical CIV proteins expressed in the CB work together to confer exquisite oxygen sensing to the ETC will help us better understand how tissue- and condition-specific CIV subunits contribute to physiological function and disease and allow us to potentially target these proteins to treat chronic diseases characterized by CB dysfunction.

scholarly journals AB0031 T HELPER 17 CELLS WERE SIGNIFICANTLY DECREASED BY MITOCHONDRIAL ELECTRON TRANSPORT CHAIN COMPLEX INHIBITOR IN PATIENTS WITH RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1318.2-1318
Author(s):  
H. R. Lee ◽  
S. J. Yoo ◽  
J. Kim ◽  
I. S. Yoo ◽  
C. K. Park ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Electron Transport ◽  
Disease Activity ◽  
Th17 Cells ◽  
Electron Transport Chain ◽  
Chain Complex ◽  
Complex Iii ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain ◽  
Healthy Control

Background:Reactive oxygen species (ROS) and T helper 17 (TH17) cells have been known to play an important role in the pathogenesis of rheumatoid arthritis (RA). However, the interrelationship between ROS and TH17 remains unclear in RAObjectives:To explore whether ROS affect TH17 cells in peripheral blood mononuclear cells (PBMC) of RA patients, we analyzed ROS expressions among T cell subsets following treatment with mitochondrial electron transport chain complex inhibitors.Methods:Blood samples were collected from 40 RA patients and 10 healthy adult volunteers. RA activity was divided according to clinical parameter DAS28. PBMC cells were obtained from the whole blood using lymphocyte separation medium density gradient centrifugation. Following PBMC was stained with Live/Dead stain dye, cells were incubated with antibodies for CD3, CD4, CD8, and CD25. After fixation and permeabilization, samples were stained with antibodies for FoxP3 and IL-17A. MitoSox were used for mitochondrial specific staining.Results:The frequency of TH17 cells was increased by 4.83 folds in moderate disease activity group (5.1>DAS28≥3.2) of RA patients compared to healthy control. Moderate RA activity patients also showed higher ratio of TH17/Treg than healthy control (3.57 folds). All RA patients had elevated expression of mitochondrial specific ROS than healthy control. When PBMC cells were treated with 2.5uM of antimycin A (mitochondrial electron transport chain complex III inhibitor) for 16 h, the frequency of TH17 cells was significantly decreased.Conclusion:The mitochondrial electron transport chain complex III inhibitor markedly downregulated the frequency of TH17 cells in moderate disease activity patients with RA. These findings provide a novel approach to regulate TH17 function in RA through mitochondrial metabolism related ROS production.References:[1]Szekanecz, Z., et al., New insights in synovial angiogenesis. Joint Bone Spine, 2010. 77(1): p. 13-9.[2]Prevoo, M.L., et al., Modified disease activity scores that include twenty-eight-joint counts. Development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum, 1995. 38(1): p. 44-8.Disclosure of Interests:None declared

scholarly journals Anticancer gold(iii)-bisphosphine complex alters the mitochondrial electron transport chain to induce in vivo tumor inhibition

2021 ◽  
Author(s):  
Jong Hyun Kim ◽  
Samuel Ofori ◽  
Sean Parkin ◽  
Hemendra Vekaria ◽  
Patrick G. Sullivan ◽  
...  
Keyword(s):  
Electron Transport ◽  
Metal Complexes ◽  
Electron Transport Chain ◽  
Chemical Diversity ◽  
Mitochondrial Electron Transport Chain ◽  
Generate Functional ◽  
Tumor Inhibition ◽  
Transport Chain

Expanding the chemical diversity of metal complexes provides a robust platform to generate functional bioactive reagents.

New inhibitors of Complex I of the mitochondrial electron transport chain with activity as pesticides

1994 ◽  
Vol 22 (1) ◽  
pp. 230-233 ◽  
Author(s):  
Robert M. Hollingworth ◽  
Kabeer I. Ahammadsahib ◽  
G. Gadelhak ◽  
J. L. McLaughlin
Keyword(s):  
Electron Transport ◽  
Complex I ◽  
Electron Transport Chain ◽  
Mitochondrial Electron Transport Chain ◽  
Transport Chain
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