Mitochondrial iron metabolism and its role in diseases

Gao, Jiayin; Zhou, Qi; Wu, Di; Chen, Linxi

doi:10.1016/j.cca.2020.12.005

Cited by 67 publications

(45 citation statements)

References 111 publications

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“…Once in the cell, iron is mostly utilized in mitochondria as the cofactor of enzymes involved in energy production. A detailed description of mitochondrial iron metabolism is covered in other recent reviews [2,3]. Concisely, iron enters the outer mitochondrial membrane via a still-unknown chaperone or by direct contact with endosomes, a pathway called kiss-and-run, or by a mitochondrial form of divalent metal transporter 1 [4].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

Levi

Ripamonti

Dardi

et al. 2021

Cells

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In 2001, a new type of human ferritin was identified by searching for homologous sequences to H-ferritin in the human genome. After the demonstration that this ferritin is located specifically in the mitochondrion, it was called mitochondrial ferritin. Studies on the properties of this new type of ferritin have been limited by its very high homology with the cytosolic H-ferritin, which is expressed at higher levels in cells. This great similarity made it difficult to obtain specific antibodies against the mitochondrial ferritin devoid of cross-reactivity with cytosolic ferritin. Thus, the knowledge of the physiological role of mitochondrial ferritin is still incomplete despite 20 years of research. In this review, we summarize the literature on mitochondrial ferritin expression regulation and its physical and biochemical properties, with particular attention paid to the differences with cytosolic ferritin and its role in physiological condition. Until now, there has been no evidence that the alteration of the mitochondrial ferritin gene is causative of any disorder; however, the identified association of the mitochondrial ferritin with some disorders is discussed.

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Section: Introductionmentioning

confidence: 99%

Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

Levi

Ripamonti

Dardi

et al. 2021

Cells

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“…While our results demonstrated exercise-induced ferritin and HO-1 reductions in the mouse cortex, ferritin levels and total iron content in muscle were elevated upon exercise with no changes in HO-1 muscular level, which may indicate unchanged labile iron in response to regular exercise in muscle. Mitochondria play an important role in iron metabolism, participating in synthesis of iron sulfur clusters and heme, with the latter molecule being essential for oxygen transport and energy production [49,50]. It is known that exercise training induces increases in skeletal muscle mitochondrial mass, and enhances oxidative muscle capacity and oxygen delivery to skeletal muscle [51].…”

Section: Discussionmentioning

confidence: 99%

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Belaya

Kucháriková

Górová

et al. 2021

IJMS

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Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear. The purpose of the study is to explore the effect of regular physical exercise on modulation of iron homeostasis in the brain and periphery of the 5xFAD mouse model of AD. By using inductively coupled plasma mass spectrometry and a variety of biochemical techniques, we measured total iron content and level of proteins essential in iron homeostasis in the brain and skeletal muscles of sedentary and exercised mice. Long-term voluntary running induced redistribution of iron resulted in altered iron metabolism and trafficking in the brain and increased iron content in skeletal muscle. Exercise reduced levels of cortical hepcidin, a key regulator of iron homeostasis, coupled with interleukin-6 (IL-6) decrease in cortex and plasma. We propose that regular exercise induces a reduction of hepcidin in the brain, possibly via the IL-6/STAT3/JAK1 pathway. These findings indicate that regular exercise modulates iron homeostasis in both wild-type and AD mice.

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“…Mitochondria are the main utilization sites of iron which are transported to the matrix to synthesize iron-sulfur clusters and heme [ 153 ]. The precise regulation of iron ions in mitochondria is essential for hemoglobin production, Fe-S cluster protein assembly and heme biosynthesis during red blood cell development [ 78 , 154 , 155 ]. It is conceivable that mitochondrial iron homeostasis is involved in various hematological diseases.…”

Section: Mitochondrial Iron Ionmentioning

confidence: 99%

“…It is conceivable that mitochondrial iron homeostasis is involved in various hematological diseases. Mitochondrial iron homeostasis and its dysfunctions have been found in sideroblastic anemia and neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, Huntington disease, and Friedreich’s ataxia [ 78 , 79 , 80 , 81 ]. Strikingly, iron overload is the primary cause of increased morbidity in thalassemia [ 156 ], but the current research on the relationship between mitochondrial iron homeostasis and thalassemia is very rare.…”

Section: Mitochondrial Iron Ionmentioning

confidence: 99%

Mitochondrial Metal Ion Transport in Cell Metabolism and Disease

Wang

et al. 2021

IJMS

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Mitochondria are vital to life and provide biological energy for other organelles and cell physiological processes. On the mitochondrial double layer membrane, there are a variety of channels and transporters to transport different metal ions, such as Ca2+, K+, Na+, Mg2+, Zn2+ and Fe2+/Fe3+. Emerging evidence in recent years has shown that the metal ion transport is essential for mitochondrial function and cellular metabolism, including oxidative phosphorylation (OXPHOS), ATP production, mitochondrial integrity, mitochondrial volume, enzyme activity, signal transduction, proliferation and apoptosis. The homeostasis of mitochondrial metal ions plays an important role in maintaining mitochondria and cell functions and regulating multiple diseases. In particular, channels and transporters for transporting mitochondrial metal ions are very critical, which can be used as potential targets to treat neurodegeneration, cardiovascular diseases, cancer, diabetes and other metabolic diseases. This review summarizes the current research on several types of mitochondrial metal ion channels/transporters and their functions in cell metabolism and diseases, providing strong evidence and therapeutic strategies for further insights into related diseases.

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Mitochondrial iron metabolism and its role in diseases

Cited by 67 publications

References 111 publications

Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Mitochondrial Metal Ion Transport in Cell Metabolism and Disease

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