0
selected
-
1.
Insight of the role of mitochondrial calcium homeostasis in hepatic insulin resistance.
Dong, Z, Yao, X
Mitochondrion. 2022;:128-138
Abstract
Due to the rapid rise in the prevalence of chronic metabolic disease, more and more clinicians and basic medical researchers focus their eyesight on insulin resistance (IR), an early and central event of metabolic diseases. The occurrence and development of IR are primarily caused by excessive energy intake and reduced energy consumption. Liver is the central organ that controls glucose homeostasis, playing a considerable role in systemic IR. Decreased capacity of oxidative metabolism and mitochondrial dysfunction are being blamed as the direct reason for the development of IR. Mitochondrial Ca2+ plays a fundamental role in maintaining proper mitochondrial function and redox stability. The maintaining of mitochondrial Ca2+ homeostasis requires the cooperation of ion channels in the inner and outer membrane of mitochondria, such as mitochondrial calcium uniporter complex (MCUC) and voltage-dependent anion channels (VDACs). In addition, the crosstalk between the endoplasmic reticulum (ER), lysosome and plasma membrane with mitochondria is also significant for mitochondrial calcium homeostasis, which is responsible for an efficient network of cellular Ca2+ signaling. Here, we review the recent progression in the research about the regulation factors for mitochondrial Ca2+ and how the dysregulation of mitochondrial Ca2+ homeostasis is involved in the pathogenesis of hepatic IR, providing a new perspective for further exploring the role of ion in the onset and development of IR.
-
2.
New Insights into Molecular Mechanisms Mediating Adaptation to Exercise; A Review Focusing on Mitochondrial Biogenesis, Mitochondrial Function, Mitophagy and Autophagy.
Roberts, FL, Markby, GR
Cells. 2021;(10)
Abstract
Exercise itself is fundamental for good health, and when practiced regularly confers a myriad of metabolic benefits in a range of tissues. These benefits are mediated by a range of adaptive responses in a coordinated, multi-organ manner. The continued understanding of the molecular mechanisms of action which confer beneficial effects of exercise on the body will identify more specific pathways which can be manipulated by therapeutic intervention in order to prevent or treat various metabolism-associated diseases. This is particularly important as exercise is not an available option to all and so novel methods must be identified to confer the beneficial effects of exercise in a therapeutic manner. This review will focus on key emerging molecular mechanisms of mitochondrial biogenesis, autophagy and mitophagy in selected, highly metabolic tissues, describing their regulation and contribution to beneficial adaptations to exercise.
-
3.
Mitochondrial Protection and Anti-inflammatory Effects Induced by Emodin in the Human Neuroblastoma SH-SY5Y Cells Exposed to Hydrogen Peroxide: Involvement of the AMPK/Nrf2 Signaling Pathway.
de Oliveira, MR, de Souza, ICC, Brasil, FB
Neurochemical research. 2021;(3):482-493
Abstract
Emodin (EM; 1,3,8-trihydroxy-6-methylanthracene-9,10-dione; C15H10O5) is an anthraquinone and exerts cytoprotective effects, as observed in both in vitro and in vivo experimental models. Mitochondrial dysfunction induced by reactive species plays a central role in the onset and progression of different human diseases. Thus, we have tested here whether a pretreatment (for 4 h) with EM (at 40 µM) would be able to promote mitochondrial protection in the human neuroblastoma SH-SY5Y cells exposed to the pro-oxidant agent hydrogen peroxide (H2O2). We found that the pretreatment with EM suppressed the effects of H2O2 on the activity of the mitochondrial complexes I and V, as well as on the production of adenosine triphosphate (ATP) and on the mitochondrial membrane potential (MMP). EM also prevented the H2O2-induced collapse in the tricarboxylic acid cycle (TCA) function. An anti-inflammatory role for EM was also observed in this experimental model, since this anthraquinone decreased the secretion of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) by the H2O2-challenged cells. Inhibition of the adenosine monophosphate-activated protein kinase (AMPK) or silencing of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) abolished the protection induced by EM in the H2O2-treated cells. Therefore, EM prevented the H2O2-induced mitochondrial dysfunction and pro-inflammatory state in the SH-SY5Y cells by an AMPK/Nrf2-dependent manner.
-
4.
Intricate role of mitochondrial calcium signalling in mitochondrial quality control for regulation of cancer cell fate.
Patra, S, Mahapatra, KK, Praharaj, PP, Panigrahi, DP, Bhol, CS, Mishra, SR, Behera, BP, Singh, A, Jena, M, Bhutia, SK
Mitochondrion. 2021;:230-240
Abstract
Mitochondrial quality control is crucial for sustaining cellular maintenance. Mitochondrial Ca2+ plays an important role in the maintenance of mitochondrial quality control through regulation of mitochondrial dynamics, mitophagy and mitochondrial biogenesis for preserving cellular homeostasis. The regulation of this dynamic interlink between these mitochondrial networks and mitochondrial Ca2+ appears indispensable for the adaptation of cells under external stimuli. Moreover, dysregulation of mitochondrial Ca2+ divulges impaired mitochondrial control that results in several pathological conditions such as cancer. Hence this review untangles the interplay between mitochondrial Ca2+ and quality control that govern mitochondrial health and mitochondrial coordinates in the development of cancer.
-
5.
Advancing organelle genome transformation and editing for crop improvement.
Li, S, Chang, L, Zhang, J
Plant communications. 2021;(2):100141
Abstract
Plant cells contain three organelles that harbor DNA: the nucleus, plastids, and mitochondria. Plastid transformation has emerged as an attractive platform for the generation of transgenic plants, also referred to as transplastomic plants. Plastid genomes have been genetically engineered to improve crop yield, nutritional quality, and resistance to abiotic and biotic stresses, as well as for recombinant protein production. Despite many promising proof-of-concept applications, transplastomic plants have not been commercialized to date. Sequence-specific nuclease technologies are widely used to precisely modify nuclear genomes, but these tools have not been applied to edit organelle genomes because the efficient homologous recombination system in plastids facilitates plastid genome editing. Unlike plastid transformation, successful genetic transformation of higher plant mitochondrial genome transformation was tested in several research group, but not successful to date. However, stepwise progress has been made in modifying mitochondrial genes and their transcripts, thus enabling the study of their functions. Here, we provide an overview of advances in organelle transformation and genome editing for crop improvement, and we discuss the bottlenecks and future development of these technologies.
-
6.
What is the Role of Lipid Membrane-embedded Quinones in Mitochondria and Chloroplasts? Chemiosmotic Q-cycle versus Murburn Reaction Perspective.
Manoj, KM, Gideon, DA, Parashar, A
Cell biochemistry and biophysics. 2021;(1):3-10
Abstract
Quinones are found in the lipid membranes of prokaryotes like E. coli and cyanobacteria, and are also abundant in eukaryotic mitochondria and chloroplasts. They are intricately involved in the reaction mechanism of redox phosphorylations. In the Mitchellian chemiosmotic school of thought, membrane-lodged quinones are perceived as highly mobile conveyors of two-electron equivalents from the first leg of Electron Transport Chain (ETC) to the 'second pit-stop' of Cytochrome bc1 or b6f complex (CBC), where they undergo a regenerative 'Q-cycle'. In Manoj's murburn mechanism, the membrane-lodged quinones are perceived as relatively slow-moving one- or two- electron donors/acceptors, enabling charge separation and the CBC resets a one-electron paradigm via 'turbo logic'. Herein, we compare various purviews of the two mechanistic schools with respect to: constraints in mobility, protons' availability, binding of quinones with proteins, structural features of the protein complexes, energetics of reaction, overall reaction logic, etc. From various perspectives, the murburn mechanism appeals as a viable alternative explanation well-rooted in thermodynamics/kinetics and one which lends adequate structure-function correlations for the roles of quinones, lipid membrane and associated proteins.
-
7.
New focuses on roles of communications between endoplasmic reticulum and mitochondria in identification of biomarkers and targets.
Zhang, L, Yan, F, Li, L, Fu, H, Song, D, Wu, D, Wang, X
Clinical and translational medicine. 2021;(11):e626
Abstract
The communication between endoplasmic reticulum (ER) and mitochondria (Mt) plays important roles in maintenance of intra- and extra-cellular microenvironment, metabolisms, signaling activities and cell-cell communication. The present review aims to overview the advanced understanding about roles of ER-Mt structural contacts, molecular interactions and chemical exchanges, signal transmissions and inter-organelle regulations in ER-Mt communication. We address how the ER-Mt communication contributes to the regulation of lipid, amino acid and glucose metabolisms by enzymes, transporters and regulators in the process of biosynthesis. We specially emphasize the importance of deep understanding about molecular mechanisms of ER-Mt communication for identification and development of biology-specific, disease-specific and metabolism-specific biomarkers and therapeutic targets for human diseases. The inhibitors and modulators of the ER-Mt communication are categorized according to therapeutic targets. Rapid development of biotechnologies will provide new insights for spatiotemporally understanding the molecular mechanisms of ER-Mt communication.
-
8.
[Fe-S] biogenesis and unusual assembly of the ISC scaffold complex in the Plasmodium falciparum mitochondrion.
Mohammad Sadik, , Mohammad Afsar, , Ramachandran, R, Habib, S
Molecular microbiology. 2021;(2):606-623
-
-
Free full text
-
Abstract
The malaria parasite harbors two [Fe-S] biogenesis pathways of prokaryotic origin-the SUF and ISC systems in the apicoplast and mitochondrion, respectively. While the SUF machinery has been delineated, there is little experimental evidence on the ISC pathway. We confirmed mitochondrial targeting of Plasmodium falciparum ISC proteins followed by analyses of cysteine desulfurase, scaffold, and [Fe-S]-carrier components. PfIscU functioned as the scaffold in complex with the PfIscS-PfIsd11 cysteine desulfurase and could directly assemble [4Fe-4S] without prior [2Fe-2S] formation seen in other homologs. Small angle X-ray scattering and spectral studies showed that PfIscU, a trimer, bound one [4Fe-4S]. In a deviation from reported complexes from other organisms, the P. falciparum desulfurase-scaffold complex assembled around a PfIscS tetramer instead of a dimer, resulting in a symmetric hetero-hexamer [2× (2PfIscS-2PfIsd11-2PfIscU)]. PfIscU directly transferred [4Fe-4S] to the apo-protein aconitase B thus abrogating the requirement of intermediary proteins for conversion of [2Fe-2S] to [4Fe-4S] before transfer to [4Fe-4S]-recipients. Among the putative cluster-carriers, PfIscA2 was more efficient than PfNifU-like protein; PfIscA1 primarily bound iron, suggesting its potential role as a Fe2+ carrier/donor. Our results identify the core P. falciparum ISC machinery and reveal unique features compared with those in bacteria or yeast and human mitochondria.
-
9.
Mitochondrial Ferritin: Its Role in Physiological and Pathological Conditions.
Levi, S, Ripamonti, M, Dardi, M, Cozzi, A, Santambrogio, P
Cells. 2021;(8)
Abstract
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.
-
10.
Mitochondrial dysfunction as a critical event in the pathophysiology of bipolar disorder.
Scaini, G, Andrews, T, Lima, CNC, Benevenuto, D, Streck, EL, Quevedo, J
Mitochondrion. 2021;:23-36
-
-
Free full text
-
Abstract
The understanding of the pathophysiology of bipolar disorder (BD) remains modest, despite recent advances in neurobiological research. The mitochondrial dysfunction hypothesis of bipolar disorder has been corroborated by several studies involving postmortem brain analysis, neuroimaging, and specific biomarkers in both rodent models and humans. Evidence suggests that BD might be related to abnormal mitochondrial morphology and dynamics, neuroimmune dysfunction, and atypical mitochondrial metabolism and oxidative stress pathways. Mitochondrial dysfunction in mood disorders is also associated with abnormal Ca2+ levels, glutamate excitotoxicity, an imbalance between pro- and antiapoptotic proteins towards apoptosis, abnormal gene expression of electron transport chain complexes, and decreased ATP synthesis. This paper aims to review and discuss the implications of mitochondrial dysfunction in BD etiology and to explore mitochondria as a potential target for novel therapeutic agents.