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Mitochondrion May 2023Pathogenesis and salugenesis are the first and second stages of the two-stage problem of disease production and health recovery. Salugenesis is the automatic,... (Review)
Review
Pathogenesis and salugenesis are the first and second stages of the two-stage problem of disease production and health recovery. Salugenesis is the automatic, evolutionarily conserved, ontogenetic sequence of molecular, cellular, organ system, and behavioral changes that is used by living systems to heal. It is a whole-body process that begins with mitochondria and the cell. The stages of salugenesis define a circle that is energy- and resource-consuming, genetically programmed, and environmentally responsive. Energy and metabolic resources are provided by mitochondrial and metabolic transformations that drive the cell danger response (CDR) and create the three phases of the healing cycle: Phase 1-Inflammation, Phase 2-Proliferation, and Phase 3-Differentiation. Each phase requires a different mitochondrial phenotype. Without different mitochondria there can be no healing. The rise and fall of extracellular ATP (eATP) signaling is a key driver of the mitochondrial and metabolic reprogramming required to progress through the healing cycle. Sphingolipid and cholesterol-enriched membrane lipid rafts act as rheostats for tuning cellular sensitivity to purinergic signaling. Abnormal persistence of any phase of the CDR inhibits the healing cycle, creates dysfunctional cellular mosaics, causes the symptoms of chronic disease, and accelerates the process of aging. New research reframes the rising tide of chronic disease around the world as a systems problem caused by the combined action of pathogenic triggers and anthropogenic factors that interfere with the mitochondrial functions needed for healing. Once chronic pain, disability, or disease is established, salugenesis-based therapies will start where pathogenesis-based therapies end.
Topics: Humans; Mitochondria; Energy Metabolism; Chronic Disease; Signal Transduction
PubMed: 37120082
DOI: 10.1016/j.mito.2023.04.003 -
Annual Review of Physiology 2016Permanent residency in the eukaryotic cell pressured the prokaryotic mitochondrial ancestor to strategize for intracellular living. Mitochondria are able to autonomously... (Review)
Review
Permanent residency in the eukaryotic cell pressured the prokaryotic mitochondrial ancestor to strategize for intracellular living. Mitochondria are able to autonomously integrate and respond to cellular cues and demands by remodeling their morphology. These processes define mitochondrial dynamics and inextricably link the fate of the mitochondrion and that of the host eukaryote, as exemplified by the human diseases that result from mutations in mitochondrial dynamics proteins. In this review, we delineate the architecture of mitochondria and define the mechanisms by which they modify their shape. Key players in these mechanisms are discussed, along with their role in manipulating mitochondrial morphology during cellular action and development. Throughout, we highlight the evolutionary context in which mitochondrial dynamics emerged and consider unanswered questions whose dissection might lead to mitochondrial morphology-based therapies.
Topics: Animals; Humans; Membrane Fusion; Mitochondria; Mitochondrial Dynamics; Mitochondrial Membranes; Mitochondrial Proteins
PubMed: 26667075
DOI: 10.1146/annurev-physiol-021115-105011 -
Seminars in Cell & Developmental Biology Feb 2020Mitochondria are the key energy-producing organelles and cellular source of reactive species. They are responsible for managing cell life and death by a balanced... (Review)
Review
Mitochondria are the key energy-producing organelles and cellular source of reactive species. They are responsible for managing cell life and death by a balanced homeostasis passing through a network of structures, regulated principally via fission and fusion. Herein we discuss about the most advanced findings considering mitochondria as dynamic biophysical systems playing compelling roles in the regulation of energy metabolism in both physiologic and pathologic processes controlling cell death and survival. Precisely, we focus on the mitochondrial commitment to the onset, maintenance and counteraction of apoptosis, autophagy and senescence in the bioenergetic reprogramming of cancer cells. In this context, looking for a pharmacological manipulation of cell death processes as a successful route for future targeted therapies, there is major biotechnological challenge in underlining the location, function and molecular mechanism of mitochondrial proteins. Based on the critical role of mitochondrial functions for cellular health, a better knowledge of the main molecular players in mitochondria disfunction could be decisive for the therapeutical control of degenerative diseases, including cancer.
Topics: Animals; Apoptosis; Autophagy; Cellular Senescence; Humans; Mitochondria
PubMed: 31154010
DOI: 10.1016/j.semcdb.2019.05.022 -
Mitochondrion Sep 2021There is growing scientific interest to develop scalable biological measures that capture mitochondrial (dys)function. Mitochondria have their own genome, the... (Review)
Review
There is growing scientific interest to develop scalable biological measures that capture mitochondrial (dys)function. Mitochondria have their own genome, the mitochondrial DNA (mtDNA). It has been proposed that the number of mtDNA copies per cell (mtDNA copy number; mtDNAcn) reflects mitochondrial health. The common availability of stored DNA material or existing DNA sequencing data, especially from blood and other easy-to-collect samples, has made its quantification a popular approach in clinical and epidemiological studies. However, the interpretation of mtDNAcn is not univocal, and either a reduction or elevation in mtDNAcn can indicate dysfunction. The major determinants of blood-derived mtDNAcn are the heterogeneous cell type composition of leukocytes and platelet abundance, which can change with time of day, aging, and with disease. Hematopoiesis is a likely driver of blood mtDNAcn. Here we discuss the rationale and available methods to quantify mtDNAcn, the influence of blood cell type variations, and consider important gaps in knowledge that need to be resolved to maximize the scientific value around the investigation of blood mtDNAcn.
Topics: DNA Copy Number Variations; DNA, Mitochondrial; Humans; Mitochondria
PubMed: 34157430
DOI: 10.1016/j.mito.2021.06.010 -
Molecular Cell Mar 2023Mitochondria have emerged as signaling organelles with roles beyond their well-established function in generating ATP and metabolites for macromolecule synthesis....
Mitochondria have emerged as signaling organelles with roles beyond their well-established function in generating ATP and metabolites for macromolecule synthesis. Healthy mitochondria integrate various physiologic inputs and communicate signals that control cell function or fate as well as adaptation to stress. Dysregulation of these mitochondrial signaling networks are linked to pathology. Here we outline a few modes of signaling between the mitochondrion and the cytoplasm. To view this SnapShot, open or download the PDF.
Topics: Mitochondria; Signal Transduction; Cytoplasm; Organelles; Acclimatization
PubMed: 36931250
DOI: 10.1016/j.molcel.2023.01.008 -
Mitochondrion Jul 2018
Topics: Animals; Energy Metabolism; Humans; Immunity, Innate; Mitochondria; Mitochondrial Dynamics; Periodicals as Topic; Signal Transduction
PubMed: 29887010
DOI: 10.1016/j.mito.2018.05.002 -
Journal of Enzyme Inhibition and... Dec 2021COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes... (Review)
Review
COVID-19, a pandemic disease caused by a viral infection, is associated with a high mortality rate. Most of the signs and symptoms, e.g. cytokine storm, electrolytes imbalances, thromboembolism, etc., are related to mitochondrial dysfunction. Therefore, targeting mitochondrion will represent a more rational treatment of COVID-19. The current work outlines how COVID-19's signs and symptoms are related to the mitochondrion. Proper understanding of the underlying causes might enhance the opportunity to treat COVID-19.
Topics: Antiviral Agents; COVID-19; Humans; Mitochondria; SARS-CoV-2; COVID-19 Drug Treatment
PubMed: 34107824
DOI: 10.1080/14756366.2021.1937144 -
Toxicology in Vitro : An International... Feb 2019The aim of this study was to investigate the effects of excessive copper (Cu)-induced cytotoxicity on oxidative stress and mitochondrial apoptosis in chicken...
The aim of this study was to investigate the effects of excessive copper (Cu)-induced cytotoxicity on oxidative stress and mitochondrial apoptosis in chicken hepatocytes. Chicken hepatocytes were cultured in medium in the absence and presence of copper sulfate (CuSO) (10, 50, 100 μM), in N-acetyl-L-cysteine (NAC) (1 mM), and the combination of CuSO and NAC for 24 h. Morphologic observation and function, reactive oxygen species (ROS) level, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and apoptosis-related mRNA and protein levels were determined. These results indicated that excessive Cu could induce release of intracellular lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and alanine aminotransferase (ALT); increase levels of ROS, superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), lipid peroxidation (LPO), and NO; decrease glutathione (GSH) content and MMP; upregulated Bak1, Bax, CytC, and Caspase3 mRNA and protein expression, inhibited Bcl2 mRNA and protein expression, and induced cell apoptosis in a dose effect. The Cu-caused changes of all above factors were alleviated by treatment with NAC. These results suggested that excessive Cu could induce oxidative stress and apoptosis via mitochondrial pathway in chicken hepatocytes.
Topics: Animals; Apoptosis; Cells, Cultured; Chickens; Copper; Hepatocytes; Mitochondria; Oxidative Stress
PubMed: 30389602
DOI: 10.1016/j.tiv.2018.10.017 -
Journal of Molecular and Cellular... Jan 2015This is an exciting time in mitochondrial biology. The mitochondrion is finally beginning to reveal some of its long held secrets. The scientific community has started...
This is an exciting time in mitochondrial biology. The mitochondrion is finally beginning to reveal some of its long held secrets. The scientific community has started to identify at the molecular level some of the key channels and transporters that have been well studied biochemically, but which have escaped molecular identification. This special issue provides state-of-the art reviews and original articles on the mitochondrial permeability transition pore (mPTP), regulation of mitochondrial calcium homeostasis and regulation of mitochondrial dynamics.
Topics: Humans; Mitochondria
PubMed: 25463271
DOI: 10.1016/j.yjmcc.2014.11.016 -
MBio Aug 2021Apicomplexan parasites, such as Toxoplasma gondii and Plasmodium falciparum, are the cause of many important human and animal diseases. While T. gondii tachyzoites... (Review)
Review
Apicomplexan parasites, such as Toxoplasma gondii and Plasmodium falciparum, are the cause of many important human and animal diseases. While T. gondii tachyzoites replicate through endodyogeny, during which two daughter cells are formed within the parental cell, P. falciparum replicates through schizogony, where up to 32 parasites are formed in a single infected red blood cell and even thousands of daughter cells during mosquito- or liver-stage development. These processes require a tightly orchestrated division and distribution over the daughter parasites of one-per-cell organelles such as the mitochondrion and apicoplast. Although proper organelle segregation is highly essential, the molecular mechanism and the key proteins involved remain largely unknown. In this review, we describe organelle dynamics during cell division in T. gondii and P. falciparum, summarize the current understanding of the molecular mechanisms underlying organelle fission in these parasites, and introduce candidate fission proteins.
Topics: Animals; Apicoplasts; Erythrocytes; Humans; Mitochondria; Parasites; Plasmodium falciparum; Protozoan Proteins; Toxoplasma
PubMed: 34425697
DOI: 10.1128/mBio.01409-21