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Topic Review
Mitochondrion Structure and Function
Mitochondria are subcellular organelles involved in essential cellular functions, including cytosolic calcium regulation, cell apoptosis, and reactive oxygen species production. They are the site of important biochemical pathways, including the tricarboxylic acid cycle, parts of the ureagenesis cycle, or haem synthesis.
  • 497
  • 15 Mar 2023
Topic Review
Mitochondrial Volume Regulation and Swelling Mechanisms in Cardiomyocytes
Mitochondrion, known as the “powerhouse” of the cell, regulates ion homeostasis, redox state, cell proliferation and differentiation, and lipid synthesis. The inner mitochondrial membrane (IMM) controls mitochondrial metabolism and function. It possesses high levels of proteins that account for ~70% of the membrane mass and are involved in the electron transport chain, oxidative phosphorylation, energy transfer, and ion transport, among others. The mitochondrial matrix volume plays a crucial role in IMM remodeling. Several ion transport mechanisms, particularly K+ and Ca2+, regulate matrix volume. Small increases in matrix volume through IMM alterations can activate mitochondrial respiration, whereas excessive swelling can impair the IMM topology and initiates mitochondria-mediated cell death. The opening of mitochondrial permeability transition pores, the well-characterized phenomenon with unknown molecular identity, in low- and high-conductance modes are involved in physiological and pathological increases of matrix volume.
  • 526
  • 10 Aug 2023
Topic Review
Mitochondrial VDAC1 as Therapeutic Target of Inflammation-Related Diseases
The multifunctional protein, voltage-dependent anion channel 1 (VDAC1), is located on the mitochondrial outer membrane. It is a pivotal protein that maintains mitochondrial function to power cellular bioactivities via energy generation. VDAC1 is involved in regulating energy production, mitochondrial oxidase stress, Ca2+ transportation, substance metabolism, apoptosis, mitochondrial autophagy (mitophagy), and many other functions. VDAC1 malfunction is associated with mitochondrial disorders that affect inflammatory responses, resulting in an up-regulation of the body’s defensive response to stress stimulation. Overresponses to inflammation may cause chronic diseases. Mitochondrial DNA (mtDNA) acts as a danger signal that can further trigger native immune system activities after its secretion. VDAC1 mediates the release of mtDNA into the cytoplasm to enhance cytokine levels by activating immune responses. VDAC1 regulates mitochondrial Ca2+ transportation, lipid metabolism and mitophagy, which are involved in inflammation-related disease pathogenesis. 
  • 1.0K
  • 26 Oct 2022
Topic Review
Mitochondrial Unfolded Protein Response for Therapy
The mitochondrial unfolded protein response (UPRmt) is a mechanism aimed to preserve or repair damaged mitochondria. UPRmt is responsible for maintaining mitochondrial proteostasis via mitochondrial activation of a transcriptional program in the nuclear DNA. This compensation system can be divided into three main pathways: activation of (1) chaperones, which boost refolding of misfolded proteins to restore them to their functional conformation and assist the folding of newly synthesized proteins; (2) proteases that are able to degrade aberrant proteins or aggregates; and (3) an antioxidant system that palliates ROS overproduction. Although human UPRmt is not fully understood, it is gaining relevance in a variety of physiological processes on top of its canonical function, such as ageing, oxidative stress resistance, hematopoietic stem cell maintenance, glycolysis, antibacterial immunity, coenzyme Q biosynthesis, and mitochondrial fission. Loss of mitochondrial proteostasis is the main UPRmt inducer. Accumulation of damaged proteins exceeding the protein-processing capacity of the chaperones and proteases in mitochondria would activate UPRmt, for instance. Additionally, factors interfering with mitochondrial function promote UPRmt induction. Examples of these are the inhibition of complex I by rotenone, bacterial toxins, knockdown of quality control proteins, or generation of excess ROS by paraquat.
  • 429
  • 22 Jul 2022
Topic Review
Mitochondrial Transplantation in Mitochondrial Medicine
Mitochondria are cytoplasmic double-membrane organelles defined as eukaryotic cells’ powerhouses due to their involvement in the cellular bioenergetics. In particular, mitochondrial synthesis of adenosine triphosphate (ATP) is associated with the functionality of aerobic oxidative phosphorylation (OXPHOS). In addition to energy production, mitochondria play many critical roles in cellular function and signalling, including fatty acid biosynthesis, calcium homeostasis, reactive oxygen species production, cell survival, proliferation, apoptosis, autophagy, stem cell differentiation, and regulation of the immune response. 
  • 725
  • 07 Feb 2023
Topic Review
Mitochondrial Regulation of Inflammation in Diabetic Kidney Disease
Diabetes is the leading cause of chronic kidney disease worldwide. Despite the burden, the factors contributing to the development and progression of diabetic kidney disease (DKD) remain to be fully elucidated. Increasing evidence suggests that mitochondrial dysfunction is a pathological mediator in DKD as the kidney is a highly metabolic organ rich in mitochondria. Furthermore, low-grade chronic inflammation also contributes to the progression of DKD, and several inflammatory biomarkers have been reported as prognostic markers to risk-stratify patients for disease progression and all-cause mortality.
  • 572
  • 23 Nov 2022
Topic Review
Mitochondrial Redox Signaling, Kidney Diseases
Redox signaling conveys external and internal signals between redox-sensitive receptors and the downstream effectors of fission machinery. Mitochondrial dynamics require the recruitment of proteins to mitochondria. Indeed, the importation of several proteins to mitochondria depends on proton electrochemical gradient H+created by ETS at the IMM, which is called the proton motive force (PMF).
  • 369
  • 21 Dec 2021
Topic Review
Mitochondrial Redox Signaling in Pulmonary Hypertension
Mitochondria are important organelles that act as a primary site to produce reactive oxygen species (ROS). Additionally, mitochondria play a pivotal role in the regulation of Ca2+ signaling, fatty acid oxidation, and ketone synthesis. Dysfunction of these signaling molecules leads to the development of pulmonary hypertension (PH), atherosclerosis, and other vascular diseases. Features of PH include vasoconstriction and pulmonary artery (PA) remodeling, which can result from abnormal proliferation, apoptosis, and migration of PA smooth muscle cells (PASMCs). These responses are mediated by increased Rieske iron–sulfur protein (RISP)-dependent mitochondrial ROS production and increased mitochondrial Ca2+ levels. Mitochondrial ROS and Ca2+ can both synergistically activate nuclear factor κB (NF-κB) to trigger inflammatory responses leading to PH, right ventricular failure, and death. 
  • 412
  • 04 Jul 2022
Topic Review
Mitochondrial Metal Ion Transport
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.
  • 741
  • 23 Jul 2021
Topic Review
Mitochondrial Metabolism and Hematopoietic Stem Cell Aging
Mitochondrial dysfunction and stem cell exhaustion are two hallmarks of aging. In the hematopoietic system, aging is linked to imbalanced immune response and reduced regenerative capacity in hematopoietic stem cells (HSCs), as well as an increased predisposition to a spectrum of diseases, including myelodysplastic syndrome and acute myeloid leukemia.
  • 535
  • 20 Oct 2021
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