Mitochondrial membrane modifications induced by adriamycin-mediated electron transport

1983 ◽  
Vol 32 (5) ◽  
pp. 889-893 ◽  
Author(s):  
E. Goormaghtigh ◽  
G. Pollakis ◽  
J.M. Ruysschaert
Keyword(s):  
Electron Transport ◽  
Mitochondrial Membrane

Anaerobic respiration sustains mitochondrial membrane potential in a prolyl hydroxylase pathway-activated cancer cell line in a hypoxic microenvironment

2014 ◽  
Vol 306 (4) ◽  
pp. C334-C342 ◽  
Author(s):  
Eiji Takahashi ◽  
Michihiko Sato
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Cell Line ◽  
Mitochondrial Membrane Potential ◽  
Cancer Cell ◽  
Mitochondrial Membrane ◽  
Cancer Cell Line ◽  
Prolyl Hydroxylase ◽  
Complex Ii ◽  
Pathway Activation

To elucidate how tumor cells produce energy in oxygen-depleted microenvironments, we studied the possibility of mitochondrial electron transport without oxygen. We produced well-controlled oxygen gradients (ΔO2) in monolayer-cultured cells. We then visualized oxygen levels and mitochondrial membrane potential (ΔΦm) in individual cells by using the red shift of green fluorescent protein (GFP) fluorescence and a cationic fluorescent dye, respectively. In this two-dimensional tissue model, ΔΦm was abolished in cells >500 μm from the oxygen source [the anoxic front (AF)], indicating limitations in diffusional oxygen delivery. This result perfectly matched GFP-determined ΔO2. In cells pretreated with dimethyloxaloylglycine (DMOG), a prolyl hydroxylase domain-containing protein (PHD) inhibitor, the AF was expanded to 1,500–2,000 μm from the source. In these cells, tissue ΔO2 was substantially decreased, indicating that PHD pathway activation suppressed mitochondrial respiration. The expansion of the AF and the reduction of ΔO2 were much more prominent in a cancer cell line (Hep3B) than in the equivalent fibroblast-like cell line (COS-7). Hence, the results indicate that PHD pathway-activated cells can sustain ΔΦm, despite significantly decreased electron flux to complex IV. Complex II inhibition abolished the effect of DMOG in expanding the AF, although tissue ΔO2 remained shallow. Separate experiments demonstrated that complex II plays a substantial role in sustaining ΔΦm in DMOG-pretreated Hep3B cells with complex III inhibition. From these results, we conclude that PHD pathway activation can sustain ΔΦm in an otherwise anoxic microenvironment by decreasing tissue ΔO2 while activating oxygen-independent electron transport in mitochondria.

scholarly journals Palmitic Acid, but Not Lauric Acid, Induces Metabolic Inflammation, Mitochondrial Fragmentation, and a Drop in Mitochondrial Membrane Potential in Human Primary Myotubes

2021 ◽  
Vol 8 ◽  
Author(s):  
Domenico Sergi ◽  
Natalie Luscombe-Marsh ◽  
Nenad Naumovski ◽  
Mahinda Abeywardena ◽  
Nathan O'Callaghan
Keyword(s):  
Insulin Resistance ◽  
Membrane Potential ◽  
Electron Transport ◽  
Mitochondrial Membrane Potential ◽  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Chain Complex ◽  
Mitochondrial Fragmentation ◽  
Metabolic Inflammation ◽  
Transport Chain

The chain length of saturated fatty acids may dictate their impact on inflammation and mitochondrial dysfunction, two pivotal players in the pathogenesis of insulin resistance. However, these paradigms have only been investigated in animal models and cell lines so far. Thus, the aim of this study was to compare the effect of palmitic (PA) (16:0) and lauric (LA) (12:0) acid on human primary myotubes mitochondrial health and metabolic inflammation. Human primary myotubes were challenged with either PA or LA (500 μM). After 24 h, the expression of interleukin 6 (IL-6) was assessed by quantitative polymerase chain reaction (PCR), whereas Western blot was used to quantify the abundance of the inhibitor of nuclear factor κB (IκBα), electron transport chain complex proteins and mitofusin-2 (MFN-2). Mitochondrial membrane potential and dynamics were evaluated using tetraethylbenzimidazolylcarbocyanine iodide (JC-1) and immunocytochemistry, respectively. PA, contrarily to LA, triggered an inflammatory response marked by the upregulation of IL-6 mRNA (11-fold; P < 0.01) and a decrease in IκBα (32%; P < 0.05). Furthermore, whereas PA and LA did not differently modulate the levels of mitochondrial electron transport chain complex proteins, PA induced mitochondrial fragmentation (37%; P < 0.001), decreased MFN-2 (38%; P < 0.05), and caused a drop in mitochondrial membrane potential (11%; P < 0.01) compared to control, with this effect being absent in LA-treated cells. Thus, LA, as opposed to PA, did not trigger pathogenetic mechanisms proposed to be linked with insulin resistance and therefore represents a healthier saturated fatty acid choice to potentially preserve skeletal muscle metabolic health.

scholarly journals Redox regulation of mitochondrial functional activity by quinones

2016 ◽  
Vol 103 (4) ◽  
pp. 439-458 ◽  
Author(s):  
NG Krylova ◽  
TA Kulahava ◽  
VT Cheschevik ◽  
IK Dremza ◽  
GN Semenkova ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Function ◽  
Mitochondrial Membrane ◽  
Reduction Potential ◽  
Electron Flow ◽  
Rat Liver Mitochondria ◽  
Ros Generation ◽  
Intact Cells

Quinones are among the rare compounds successfully used as therapeutic agents to correct mitochondrial diseases and as specific regulators of mitochondrial function within cells. The aim of the present study was to elucidate the redox-dependent effects of quinones on mitochondrial function. The functional parameters [respiratory activity, membrane potential, and reactive oxygen species (ROS) generation] of isolated rat liver mitochondria and mitochondria in intact cells were measured in the presence of eight exogenously applied quinones that differ in lipophilicity and one-electron reduction potential. The quinones affected the respiratory parameters of mitochondria, and dissipated the mitochondrial membrane potential as well as influenced (either decreased or enhanced) ROS generation, and restored the electron flow during electron transport chain inhibition. The stimulation of ROS production by juglone and 2,5-di-tert-butyl-1,4-benzoquinone was accompanied by a decrease in the acceptor control and respiration control ratios, dissipation of the mitochondrial membrane potential and induction of the reverse electron flow under succinate oxidation in isolated mitochondria. Menadione and 2,3,5-trimethyl-1,4-benzoquinone, which decreased the mitochondrial ROS generation, did not affect the mitochondrial potential and, vice versa, were capable of restoring electron transport during Complex I inhibition. In intact C6 cells, all the quinones, except for coenzyme Q10, decreased the mitochondrial membrane potential. Juglone, 1,4-benzoquinone, and menadione showed the most pronounced effects. These findings indicate that quinones with the reduction potential values E1/2 in the range from −99 to −260 mV were effective redox regulators of mitochondrial electron transport.

scholarly journals Bcl-2 Family Members and Functional Electron Transport Chain Regulate Oxygen Deprivation-Induced Cell Death

2002 ◽  
Vol 22 (1) ◽  
pp. 94-104 ◽  
Author(s):  
David S. McClintock ◽  
Matthew T. Santore ◽  
Vivian Y. Lee ◽  
Joslyn Brunelle ◽  
G. R. Scott Budinger ◽  
...  
Keyword(s):  
Cell Death ◽  
Membrane Potential ◽  
Electron Transport ◽  
Mitochondrial Membrane Potential ◽  
Electron Transport Chain ◽  
Mitochondrial Membrane ◽  
Family Members ◽  
Oxygen Deprivation ◽  
Caspase 9 ◽  
Transport Chain

ABSTRACT The mechanisms underlying cell death during oxygen deprivation are unknown. We report here a model for oxygen deprivation-induced apoptosis. The death observed during oxygen deprivation involves a decrease in the mitochondrial membrane potential, followed by the release of cytochrome c and the activation of caspase-9. Bcl-XL prevented oxygen deprivation-induced cell death by inhibiting the release of cytochrome c and caspase-9 activation. The ability of Bcl-XL to prevent cell death was dependent on allowing the import of glycolytic ATP into the mitochondria to generate an inner mitochondrial membrane potential through the F1F0-ATP synthase. In contrast, although activated Akt has been shown to inhibit apoptosis induced by a variety of apoptotic stimuli, it did not prevent cell death during oxygen deprivation. In addition to Bcl-XL, cells devoid of mitochondrial DNA (ρ° cells) that lack a functional electron transport chain were resistant to oxygen deprivation. Further, murine embryonic fibroblasts from bax −/− bak −/− mice did not die in response to oxygen deprivation. These data suggest that when subjected to oxygen deprivation, cells die as a result of an inability to maintain a mitochondrial membrane potential through the import of glycolytic ATP. Proapoptotic Bcl-2 family members and a functional electron transport chain are required to initiate cell death in response to oxygen deprivation.

Monitoring PO2 by the Carotid Chemoreceptor

Physiology ◽  
1990 ◽  
Vol 5 (6) ◽  
pp. 229-233 ◽  
Author(s):  
TJ Biscoe
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Mitochondrial Membrane Potential ◽  
Carotid Body ◽  
Mitochondrial Membrane ◽  
Oxygen Sensor ◽  
Sensory Transduction

The carotid body is a major oxygen sensor in the mammal. Measurements of cell electrophysiology, (Ca2+)i, mitochondrial membrane potential, and intracellular NADH suggest that specialized mitochondrial electron transport underlies sensory transduction.

Regulation of the mitochondrial permeability transition by matrix Ca2+ and voltage during anoxia/reoxygenation

2001 ◽  
Vol 280 (3) ◽  
pp. C517-C526 ◽  
Author(s):  
Paavo Korge ◽  
Henry M. Honda ◽  
James N. Weiss
Keyword(s):  
Membrane Potential ◽  
Electron Transport ◽  
Cyclosporin A ◽  
Mitochondrial Membrane ◽  
Mitochondrial Permeability Transition ◽  
Permeability Transition ◽  
Mitochondrial Permeability ◽  
Matrix Volume ◽  
Reoxygenation Injury ◽  
Load Size

We studied the interplay between matrix Ca2+ concentration ([Ca2+]) and mitochondrial membrane potential (Δψ) in regulation of the mitochondrial permeability transition (MPT) during anoxia and reoxygenation. Without Ca2+loading, anoxia caused near-synchronous Δψ dissipation, mitochondrial Ca2+ efflux, and matrix volume shrinkage when a critically low Po 2 was reached, which was rapidly reversible upon reoxygenation. These changes were related to electron transport inhibition, not MPT. Cyclosporin A-sensitive MPT did occur when extramitochondrial [Ca2+] was increased to promote significant Ca2+ uptake during anoxia, depending on the Ca2+ load size and ability to maintain Δψ. However, when [Ca2+] was increased after complete Δψ dissipation, MPT did not occur until reoxygenation, at which time reactivation of electron transport led to partial Δψ regeneration. In the setting of elevated extramitochondrial Ca2+, this enhanced matrix Ca2+ uptake while promoting MPT because of less than full recovery of Δψ. The interplay between Δψ and matrix [Ca2+] in accelerating or inhibiting MPT during anoxia/reoxygenation has implications for preventing reoxygenation injury associated with MPT.

Sign in / Sign up

Export Citation Format

Share Document