Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury

Kulek, Andrew; Anzell, Anthony R.; Wider, Joseph M.; Sanderson, Thomas H.; Przyklenk, Karin

doi:10.3390/cells9010214

Cited by 59 publications

(34 citation statements)

References 347 publications

(615 reference statements)

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“…The aforementioned energetic breakdown of the cell provokes a mitochondrial depolarization and the closing of mitochondrial permeability transition pore (MPTP), which is accompanied by increases in lactate, succinate and other ROS precursors associated in this oxygen deprivation condition. In this sense, mitochondrial protection conferred by PEG35 would be a critical point in ischemias, as recently suggested by Kulek et al [48] With its potential cytoprotective effects in mind, we evaluated the benefits of PEG35 in rinse solution for graft washout after cold preservation [19]. The presence of PEG35 in rinse solution after static preservation in UW confirmed that this polymer is directly responsible for mitochondrial preservation during cold storage, including as well the concomitant activation of cytoprotective factors such as AMP-activated protein kinase (AMPK) and presumably the inherent cytoskeleton rearrangement [19].…”

Section: Static Cold Storage (Scs) and Pegmentioning

confidence: 61%

Section: Static Cold Storage (Scs) and Pegmentioning

confidence: 72%

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Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Rosello

Silva

Castro

et al. 2020

IJMS

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Organ transplantation is a multifactorial process in which proper graft preservation is a mandatory step for the success of the transplantation. Hypothermic preservation of abdominal organs is mostly based on the use of several commercial solutions, including UW, Celsior, HTK and IGL-1. The presence of the oncotic agents HES (in UW) and PEG35 (in IGL-1) characterize both solution compositions, while HTK and Celsior do not contain any type of oncotic agent. Polyethylene glycols (PEGs) are non-immunogenic, non-toxic and water-soluble polymers, which present a combination of properties of particular interest in the clinical context of ischemia-reperfusion injury (IRI): they limit edema and nitric oxide induction and modulate immunogenicity. Besides static cold storage (SCS), there are other strategies to preserve the organ, such as the use of machine perfusion (MP) in dynamic preservation strategies, which increase graft function and survival as compared to the conventional static hypothermic preservation. Here we report some considerations about using PEG35 as a component of perfusates for MP strategies (such as hypothermic oxygenated perfusion, HOPE) and its benefits for liver graft preservation. Improved liver preservation is closely related to mitochondria integrity, making this organelle a good target to increase graft viability, especially in marginal organs (e.g., steatotic livers). The final goal is to increase the pool of suitable organs, and thereby shorten patient waiting lists, a crucial problem in liver transplantation.

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Section: Static Cold Storage (Scs) and Pegmentioning

confidence: 61%

Section: Static Cold Storage (Scs) and Pegmentioning

confidence: 72%

Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Rosello

Silva

Castro

et al. 2020

IJMS

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“…The important role of mitochondrial quality control mechanisms (involving the regulation of the mitochondrial fission and fusion, proteolysis and mitophagy) in the responses to H/R stress is well established in the hypoxia-sensitive mammalian models such as rodents (Kulek et al, 2020;Wang and Zhou, 2020). Earlier studies also indicate that high activity and upregulated mRNA expression of mitochondrial proteases correlates with elevated hypoxia tolerance in marine bivalves .…”

Section: Introductionmentioning

confidence: 99%

Molecular Biomarkers of the Mitochondrial Quality Control Are Differently Affected by Hypoxia-Reoxygenation Stress in Marine Bivalves Crassostrea gigas and Mytilus edulis

et al. 2020

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Coastal environments commonly experience strong oxygen fluctuations. Resulting hypoxia/reoxygenation stress can negatively affect mitochondrial functions, since oxygen deficiency impairs ATP generation, whereas a surge of oxygen causes mitochondrial damage by oxidative stress. Marine intertidal bivalves are adapted to fluctuating oxygen conditions, yet the underlying molecular mechanisms that sustain mitochondrial integrity and function during oxygen fluctuations are not yet well understood. We used targeted mRNA expression analysis to determine the potential involvement of the mitochondrial quality control mechanisms in responses to short-term hypoxia (24 h at <0.01% O2) and subsequent reoxygenation (1.5 h at 21% O2) in two hypoxia-tolerant marine bivalves, the Pacific oysters Crassostrea gigas and the blue mussels Mytilus edulis. We hypothesized that the genes involved in the mitochondrial quality control will be upregulated during hypoxia, and the less hypoxia-tolerant of the two studied species (M. edulis) will show a stronger dependence on transcriptional upregulation of these pathways than C. gigas. To test these hypotheses, mRNA expression of 17 (C. gigas) and 11 (M. edulis) marker genes involved in mitochondrial fusion, fission, proteolysis and mitophagy was analyzed in the digestive gland of M. edulis and C. gigas in normoxia and during hypoxia-reoxygenation (H/R) stress. In the mussels, the mRNA expression of the transcripts related to mitochondrial dynamics and quality control was strongly altered during H/R stress showing a shift toward fission, suppression of fusion, an increase in mitochondrial proteolysis and onset of mitophagy. These changes indicate that H/R stress induces mitochondrial injury in M. edulis requiring upregulation of the protective mechanisms to segregate the dysfunctional mitochondria by fission and degrade the oxidative damaged proteins and/or organelles. Unlike mussels, the transcript levels of all studied genes in the oysters remained at the baseline (normoxic) levels during H/R stress. This muted transcriptional response of C. gigas is in agreement with earlier findings showing better ability to maintain cellular homeostasis and higher resistance to apoptosis during H/R stress in the oysters compared with the mussels. The revealed species-specific differences in the expression of the mitochondrial quality control pathways shed light on the potentially important mechanisms of mitochondrial protection against H/R-induced damage that might contribute to hypoxia tolerance in marine bivalves.

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“…Pathological cardiac conditions resulting from ischemic cardiac injuries and occlusion of a coronary vessel induces a cascade of tissue hypoxia and cellular ATP depletion ( Peoples et al, 2019 ). A series of events may contribute to this process of ischemic and reperfusion damage to cardiac tissues with impairment of mitochondrial integrity being central to this process, including the generation of ROS, opening of the mitochondrial permeability transition pore (mPTP), and activation of intrinsic apoptosis ( Kulek et al, 2020 ). Under these drastic changes in nutrient and oxygen availabilities, a decrease in oxidative phosphorylation results in a decrease in cellular ATP, and a loss of mitochondrial membrane potential ( Murphy and Steenbergen, 2008 ).…”

Section: Association Of Cardiovascular Diseases and Mitochondrial Dysmentioning

confidence: 99%

Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease

Lin

Chen

Lin

et al. 2021

Front. Cell Dev. Biol.

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Cardiovascular diseases are one of the leading causes of death and global health problems worldwide. Multiple factors are known to affect the cardiovascular system from lifestyles, genes, underlying comorbidities, and age. Requiring high workload, metabolism of the heart is largely dependent on continuous power supply via mitochondria through effective oxidative respiration. Mitochondria not only serve as cellular power plants, but are also involved in many critical cellular processes, including the generation of intracellular reactive oxygen species (ROS) and regulating cellular survival. To cope with environmental stress, mitochondrial function has been suggested to be essential during bioenergetics adaptation resulting in cardiac pathological remodeling. Thus, mitochondrial dysfunction has been advocated in various aspects of cardiovascular pathology including the response to ischemia/reperfusion (I/R) injury, hypertension (HTN), and cardiovascular complications related to type 2 diabetes mellitus (DM). Therefore, mitochondrial homeostasis through mitochondrial dynamics and quality control is pivotal in the maintenance of cardiac health. Impairment of the segregation of damaged components and degradation of unhealthy mitochondria through autophagic mechanisms may play a crucial role in the pathogenesis of various cardiac disorders. This article provides in-depth understanding of the current literature regarding mitochondrial remodeling and dynamics in cardiovascular diseases.

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Mitochondrial Quality Control: Role in Cardiac Models of Lethal Ischemia-Reperfusion Injury

Cited by 59 publications

References 347 publications

Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Polyethylene Glycol 35 as a Perfusate Additive for Mitochondrial and Glycocalyx Protection in HOPE Liver Preservation

Molecular Biomarkers of the Mitochondrial Quality Control Are Differently Affected by Hypoxia-Reoxygenation Stress in Marine Bivalves Crassostrea gigas and Mytilus edulis

Quality Matters? The Involvement of Mitochondrial Quality Control in Cardiovascular Disease

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