The effects of iron overload on mitochondrial function, mitochondrial dynamics, and ferroptosis in cardiomyocytes

Sumneang, Natticha; Siri‐Angkul, Natthaphat; Kumfu, Sirinart; Chattipakorn, Siriporn C.

doi:10.1016/j.abb.2019.108241

Cited by 88 publications

(62 citation statements)

References 47 publications

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“…The precise mechanism of the beneficial effects of liproxstatin-1 on mitochondria involves the reduction of VDAC1 level and its oligomerization, without affecting VDAC2/3, as well as a decrease in mitochondrial ROS production by the ETC complex I (NADH:ubiquinone oxidoreductase). These results are in agreement with studies postulating that mitochondrial ROS generation is a significant contributor to ferroptosis [ 105 , 106 ]. This contrasts with the often-represented standpoint that mitochondrial damage is a secondary event in ferroptosis [ 13 , 80 ] and also opposes studies that did not observe changes in complex I ROS production in erastin-induced or ferrostatin-inhibited ferroptosis [ 12 , 63 ], suggesting that the impact of mitochondrial ROS on ferroptosis might be dependent on the specific inducer or inhibitor of ferroptosis used.…”

Section: Mitochondria and Ferroptosis In Cardiovascular Diseasessupporting

confidence: 93%

Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria

Otašević

Vučetić

Grigorov

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a recently described form of regulated cell death characterized by intracellular iron accumulation and severe lipid peroxidation due to an impaired cysteine-glutathione-glutathione peroxidase 4 antioxidant defence axis. One of the hallmarks of ferroptosis is a specific morphological phenotype characterized by extensive ultrastructural changes of mitochondria. Increasing evidence suggests that mitochondria play a significant role in the induction and execution of ferroptosis. The present review summarizes existing knowledge about the mitochondrial impact on ferroptosis in different pathological states, primarily cancer, cardiovascular diseases, and neurodegenerative diseases. Additionally, we highlight pathologies in which the ferroptosis/mitochondria relation remains to be investigated, where the process of ferroptosis has been confirmed (such as liver- and kidney-related pathologies) and those in which ferroptosis has not been studied yet, such as diabetes. We will bring attention to avenues that could be followed in future research, based on the use of mitochondria-targeted approaches as anti- and proferroptotic strategies and directed to the improvement of existing and the development of novel therapeutic strategies.

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Section: Mitochondria and Ferroptosis In Cardiovascular Diseasessupporting

confidence: 93%

Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria

Otašević

Vučetić

Grigorov

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…As shown in Figure 2, the changes in mitochondrial dynamics are associated with cell viability, apoptosis, and bioenergetic adaptations [75,76]. Mitochondrial fission is observed when mitochondria are subjected to oxidative stress-induced damage and segregates damaged mitochondria from the normal ones [77][78][79][80]. The mitochondrial fusion-fission balance is disrupted by intracellular and extracellular stress, and the fragmented mitochondria form small spheres or short rods in comparison to extensive elongated network of the normal mitochondria [20,81].…”

Section: Mitochondrial Fissionmentioning

confidence: 99%

Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

Toan

Zhou

2020

Aging

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Nutrient oversupply and mitochondrial dysfunction play central roles in nonalcoholic fatty liver disease (NAFLD). The mitochondria are the major sites of β-oxidation, a catabolic process by which fatty acids are broken down. The mitochondrial quality control (MQC) system includes mitochondrial fission, fusion, mitophagy and mitochondrial redox regulation, and is essential for the maintenance of the functionality and structural integrity of the mitochondria. Excessive and uncontrolled production of reactive oxygen species (ROS) in the mitochondria damages mitochondrial components, including membranes, proteins and mitochondrial DNA (mtDNA), and triggers the mitochondrial pathway of apoptosis. The functionality of some damaged mitochondria can be restored by fusion with normally functioning mitochondria, but when severely damaged, mitochondria are segregated from the remaining functional mitochondrial network through fission and are eventually degraded via mitochondrial autophagy, also called as mitophagy. In this review, we describe the functions and mechanisms of mitochondrial fission, fusion, oxidative stress and mitophagy in the development and progression of NAFLD.

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“…It is characterized by the accumulation of lipid peroxidation products and lethal ROS derived from iron metabolism and can be pharmacologically inhibited by iron chelators. Although the detailed mechanism by which iron overload promotes ferroptosis has yet to determined, it is reasonable to hypothesize that iron overload may drive the generation of hydroxyl radicals, which further react with liposomes to produce lipid peroxidation products and cause mitochondrial dysfunction, and eventually ferroptosis [ 310 , 311 , 312 ]. Although mitochondria have been shown to be vital regulators of iron homeostasis and ferroptosis in neurodegenerative diseases [ 313 ], more direct evidence targeting iron overload, mitochondrial dysfunction, and ferroptosis is still required.…”

Section: Molecular Mechanisms Of Metal-induced Mitochondrial Dysfunctionmentioning

confidence: 99%

Mechanisms of Metal-Induced Mitochondrial Dysfunction in Neurological Disorders

Cheng

Yang

Tao

et al. 2021

Toxics

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Metals are actively involved in multiple catalytic physiological activities. However, metal overload may result in neurotoxicity as it increases formation of reactive oxygen species (ROS) and elevates oxidative stress in the nervous system. Mitochondria are a key target of metal-induced toxicity, given their role in energy production. As the brain consumes a large amount of energy, mitochondrial dysfunction and the subsequent decrease in levels of ATP may significantly disrupt brain function, resulting in neuronal cell death and ensuing neurological disorders. Here, we address contemporary studies on metal-induced mitochondrial dysfunction and its impact on the nervous system.

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The effects of iron overload on mitochondrial function, mitochondrial dynamics, and ferroptosis in cardiomyocytes

Cited by 88 publications

References 47 publications

Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria

Ferroptosis in Different Pathological Contexts Seen through the Eyes of Mitochondria

Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

Mechanisms of Metal-Induced Mitochondrial Dysfunction in Neurological Disorders

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