Liver mitochondrial dysfunction and electron transport chain defect induced by high dietary copper in broilers

Background In complex congenital heart disease patients such as those with tetralogy of Fallot, the right ventricle (RV) is subject to pressure overload, leading to RV hypertrophy and eventually RV failure. The mechanisms that promote the transition from stable RV hypertrophy to RV failure are unknown. We evaluated the role of mitochondrial bioenergetics in the development of RV failure. Methods and Results We created a murine model of RV pressure overload by pulmonary artery banding and compared with sham‐operated controls. Gene expression by RNA‐sequencing, oxidative stress, mitochondrial respiration, dynamics, and structure were assessed in pressure overload‐induced RV failure. RV failure was characterized by decreased expression of electron transport chain genes and mitochondrial antioxidant genes (aldehyde dehydrogenase 2 and superoxide dismutase 2) and increased expression of oxidant stress markers (heme oxygenase, 4‐hydroxynonenal). The activities of all electron transport chain complexes decreased with RV hypertrophy and further with RV failure (oxidative phosphorylation: sham 552.3±43.07 versus RV hypertrophy 334.3±30.65 versus RV failure 165.4±36.72 pmol/(s×mL), P <0.0001). Mitochondrial fission protein DRP1 (dynamin 1‐like) trended toward an increase, while MFF (mitochondrial fission factor) decreased and fusion protein OPA1 (mitochondrial dynamin like GTPase) decreased. In contrast, transcription of electron transport chain genes increased in the left ventricle of RV failure. Conclusions Pressure overload‐induced RV failure is characterized by decreased transcription and activity of electron transport chain complexes and increased oxidative stress which are associated with decreased energy generation. An improved understanding of the complex processes of energy generation could aid in developing novel therapies to mitigate mitochondrial dysfunction and delay the onset of RV failure.

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Neutralization of Mitochondrial Superoxide by Superoxide Dismutase 2 Promotes Bacterial Clearance and Regulates Phagocyte Numbers in Zebrafish

Infection and Immunity ◽

10.1128/iai.02245-14 ◽

2014 ◽

Vol 83 (1) ◽

pp. 430-440 ◽

Cited By ~ 17

Author(s):

E. M. Peterman ◽

C. Sullivan ◽

M. F. Goody ◽

I. Rodriguez-Nunez ◽

J. A. Yoder ◽

...

Keyword(s):

Superoxide Dismutase ◽

Electron Transport ◽

Mitochondrial Dysfunction ◽

Electron Transport Chain ◽

Bacterial Burden ◽

Content Type ◽

Mitochondrial Ros ◽

Transport Chain ◽

Severe Infections ◽

Superoxide Dismutase 2

Mitochondria are known primarily as the location of the electron transport chain and energy production in cells. More recently, mitochondria have been shown to be signaling centers for apoptosis and inflammation. Reactive oxygen species (ROS) generated as by-products of the electron transport chain within mitochondria significantly impact cellular signaling pathways. Because of the toxic nature of ROS, mitochondria possess an antioxidant enzyme, superoxide dismutase 2 (SOD2), to neutralize ROS. If mitochondrial antioxidant enzymes are overwhelmed during severe infections, mitochondrial dysfunction can occur and lead to multiorgan failure or death.Pseudomonas aeruginosais an opportunistic pathogen that can infect immunocompromised patients. Infochemicals and exotoxins associated withP. aeruginosaare capable of causing mitochondrial dysfunction. In this work, we describe the roles of SOD2 and mitochondrial ROS regulation in the zebrafish innate immune response toP. aeruginosainfection.sod2is upregulated in mammalian macrophages and neutrophils in response to lipopolysaccharidein vitro, andsod2knockdown in zebrafish results in an increased bacterial burden. Further investigation revealed that phagocyte numbers are compromised in Sod2-deficient zebrafish. Addition of the mitochondrion-targeted ROS-scavenging chemical MitoTEMPO rescues neutrophil numbers and reduces the bacterial burden in Sod2-deficient zebrafish. Our work highlights the importance of mitochondrial ROS regulation by SOD2 in the context of innate immunity and supports the use of mitochondrion-targeted ROS scavengers as potential adjuvant therapies during severe infections.

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Electron Transport Chain Defect and Inefficient Respiration May Underlie Pulmonary Hypertension Syndrome (Ascites)-Associated Mitochondrial Dysfunction in Broilers

Poultry Science ◽

10.1093/ps/80.4.474 ◽

2001 ◽

Vol 80 (4) ◽

pp. 474-484 ◽

Cited By ~ 50

Author(s):

D. Cawthon ◽

K. Beers ◽

W.G. Bottje

Keyword(s):

Pulmonary Hypertension ◽

Electron Transport ◽

Mitochondrial Dysfunction ◽

Electron Transport Chain ◽

Pulmonary Hypertension Syndrome ◽

Transport Chain

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Dopamine and Methamphetamine Differentially Affect Electron Transport Chain Complexes and Parkin in Rat Striatum: New Insight into Methamphetamine Neurotoxicity

International Journal of Molecular Sciences ◽

10.3390/ijms23010363 ◽

2021 ◽

Vol 23 (1) ◽

pp. 363

Author(s):

Viktoriia Bazylianska ◽

Akhil Sharma ◽

Heli Chauhan ◽

Bernard Schneider ◽

Anna Moszczynska

Keyword(s):

Oxidative Stress ◽

Electron Transport ◽

Mitochondrial Dysfunction ◽

Complex I ◽

Electron Transport Chain ◽

Rat Striatum ◽

Experimental Conditions ◽

Chain Complexes ◽

Transport Chain

Methamphetamine (METH) is a highly abused psychostimulant that is neurotoxic to dopaminergic (DAergic) nerve terminals in the striatum and increases the risk of developing Parkinson’s disease (PD). In vivo, METH-mediated DA release, followed by DA-mediated oxidative stress and mitochondrial dysfunction in pre- and postsynaptic neurons, mediates METH neurotoxicity. METH-triggered oxidative stress damages parkin, a neuroprotective protein involved in PD etiology via its involvement in the maintenance of mitochondria. It is not known whether METH itself contributes to mitochondrial dysfunction and whether parkin regulates complex I, an enzymatic complex downregulated in PD. To determine this, we separately assessed the effects of METH or DA alone on electron transport chain (ETC) complexes and the protein parkin in isolated striatal mitochondria. We show that METH decreases the levels of selected complex I, II, and III subunits (NDUFS3, SDHA, and UQCRC2, respectively), whereas DA decreases the levels only of the NDUFS3 subunit in our preparations. We also show that the selected subunits are not decreased in synaptosomal mitochondria under similar experimental conditions. Finally, we found that parkin overexpression does not influence the levels of the NDUFS3 subunit in rat striatum. The presented results indicate that METH itself is a factor promoting dysfunction of striatal mitochondria; therefore, it is a potential drug target against METH neurotoxicity. The observed decreases in ETC complex subunits suggest that DA and METH decrease activities of the ETC complexes via oxidative damage to their subunits and that synaptosomal mitochondria may be somewhat “resistant” to DA- and METH-induced disruption in mitochondrial ETC complexes than perikaryal mitochondria. The results also suggest that parkin does not regulate NDUFS3 turnover in rat striatum.

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Mitochondrial dysfunction in the type 2 diabetic heart is associated with alterations in spatially distinct mitochondrial proteomes

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00267.2010 ◽

2010 ◽

Vol 299 (2) ◽

pp. H529-H540 ◽

Cited By ~ 104

Author(s):

Erinne R. Dabkowski ◽

Walter A. Baseler ◽

Courtney L. Williamson ◽

Matthew Powell ◽

Trust T. Razunguzwa ◽

...

Keyword(s):

Electron Transport ◽

Oxidative Damage ◽

Mitochondrial Dysfunction ◽

Electron Transport Chain ◽

Mitochondrial Membrane ◽

Diabetic Heart ◽

Mitochondrial Morphology ◽

Transport Chain ◽

Type 2 Diabetic

Cardiac complications and heart failure are the leading cause of death in type 2 diabetic patients. Mitochondrial dysfunction is central in the pathogenesis of the type 2 diabetic heart. However, it is unclear whether this dysfunction is specific for a particular subcellular region. The purpose of this study was to determine whether mitochondrial dysfunction in the type 2 diabetic heart is specific to a spatially distinct subset of mitochondria. We investigated mitochondrial morphology, function, and proteomic composition of subsarcolemmal mitochondria (SSM) and interfibrillar mitochondria (IFM) in 18-wk-old db/ db mice. Oxidative damage was assessed in subpopulations through the measurement of lipid peroxidation byproducts and nitrotyrosine residues. Proteomic profiles and posttranslational modifications were assessed in mitochondrial subpopulations using iTRAQ and multi-dimensional protein identification technologies, respectively. SSM from db/ db hearts had altered morphology, including a decrease in size and internal complexity, whereas db/ db IFM were increased in internal complexity. Db/ db SSM displayed decreased state 3 respiration rates, electron transport chain activities, ATP synthase activities, and mitochondrial membrane potential and increased oxidative damage, with no change in IFM. Proteomic assessment revealed a greater impact on db/ db SSM compared with db/ db IFM. Inner mitochondrial membrane proteins, including electron transport chain, ATP synthesis, and mitochondrial protein import machinery, were predominantly decreased. We provide evidence that mitochondrial dysfunction in the type 2 diabetic heart is associated with a specific subcellular locale. Furthermore, mitochondrial morphological and functional indexes are impacted differently during type 2 diabetic insult and may result from the modulation of spatially distinct mitochondrial proteomes.

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