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The Journal of Cell Biology Aug 2020Mitochondria, so much more than just being energy factories, also have the capacity to synthesize macromolecules including phospholipids, particularly cardiolipin (CL)... (Review)
Review
Mitochondria, so much more than just being energy factories, also have the capacity to synthesize macromolecules including phospholipids, particularly cardiolipin (CL) and phosphatidylethanolamine (PE). Phospholipids are vital constituents of mitochondrial membranes, impacting the plethora of functions performed by this organelle. Hence, the orchestrated movement of phospholipids to and from the mitochondrion is essential for cellular integrity. In this review, we capture recent advances in the field of mitochondrial phospholipid biosynthesis and trafficking, highlighting the significance of interorganellar communication, intramitochondrial contact sites, and lipid transfer proteins in maintaining membrane homeostasis. We then discuss the physiological functions of CL and PE, specifically how they associate with protein complexes in mitochondrial membranes to support bioenergetics and maintain mitochondrial architecture.
Topics: Animals; Biological Transport; Cardiolipins; Energy Metabolism; Humans; Mitochondria; Mitochondrial Membranes; Mitochondrial Proteins; Phosphatidylethanolamines; Phospholipids; Signal Transduction
PubMed: 32614384
DOI: 10.1083/jcb.202003131 -
Mitochondrion Mar 2020Autophagy is a ubiquitous homeostatic mechanism for the degradation or turnover of cellular components. Degradation of mitochondria via autophagy (mitophagy) is involved... (Review)
Review
Autophagy is a ubiquitous homeostatic mechanism for the degradation or turnover of cellular components. Degradation of mitochondria via autophagy (mitophagy) is involved in a number of physiological processes including cellular homeostasis, differentiation and aging. Upon stress or injury, mitophagy prevents the accumulation of damaged mitochondria and the increased steady state levels of reactive oxygen species leading to oxidative stress and cell death. A number of human diseases, particularly neurodegenerative disorders, have been linked to the dysregulation of mitophagy. In this mini-review, we aimed to review the molecular mechanisms involved in the regulation of mitophagy and their relationship with redox signaling and oxidative stress.
Topics: Aging; Humans; Mitochondria; Mitochondrial Diseases; Mitochondrial Dynamics; Mitophagy; Neurodegenerative Diseases; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species
PubMed: 31972372
DOI: 10.1016/j.mito.2020.01.002 -
Cell Calcium Dec 2021
Topics: Mitochondria
PubMed: 34784537
DOI: 10.1016/j.ceca.2021.102498 -
Journal of Molecular and Cellular... Feb 2023Mitochondrial dysfunction in heart triggers an integrated stress response (ISR) through phosphorylation of eIF2α and subsequent ATF4 activation. DAP3 Binding Cell Death...
Mitochondrial dysfunction in heart triggers an integrated stress response (ISR) through phosphorylation of eIF2α and subsequent ATF4 activation. DAP3 Binding Cell Death Enhancer 1 (DELE1) is a mitochondrial protein recently found to be critical for mediating mitochondrial stress-triggered ISR (MSR)-induced eIF2α-ATF4 pathway activation. However, the specific role of DELE1 in heart at baseline or in response to mitochondrial stress remains largely unknown. In this study, we report that DELE1 is dispensable for cardiac development and function under baseline conditions. Conversely, DELE1 is essential for mediating an adaptive response to mitochondrial dysfunction-triggered stress in the heart, playing a protective role in mitochondrial cardiomyopathy.
Topics: Humans; Phosphorylation; Mitochondria; Cardiomyopathies
PubMed: 36539111
DOI: 10.1016/j.yjmcc.2022.12.003 -
Experimental & Molecular Medicine Dec 2023Mitochondria participate in a wide range of cellular processes. One essential function of mitochondria is to be a platform for antiviral signaling proteins during the... (Review)
Review
Mitochondria participate in a wide range of cellular processes. One essential function of mitochondria is to be a platform for antiviral signaling proteins during the innate immune response to viral infection. Recently, studies have revealed that mitochondrion-derived DNAs and RNAs are recognized as non-self molecules and act as immunogenic ligands. More importantly, the cytosolic release of these mitochondrial nucleic acids (mt-NAs) is closely associated with the pathogenesis of human diseases accompanying aberrant immune activation. The release of mitochondrial DNAs (mtDNAs) via BAX/BAK activation and/or VDAC1 oligomerization activates the innate immune response and inflammasome assembly. In addition, mitochondrial double-stranded RNAs (mt-dsRNAs) are sensed by pattern recognition receptors in the cytosol to induce type I interferon expression and initiate apoptotic programs. Notably, these cytosolic mt-NAs also mediate adipocyte differentiation and contribute to mitogenesis and mitochondrial thermogenesis. In this review, we summarize recent studies of innate immune signaling pathways regulated by mt-NAs, human diseases associated with mt-NAs, and the emerging physiological roles of mt-NAs.
Topics: Humans; Nucleic Acids; Immunity, Innate; Signal Transduction; Receptors, Pattern Recognition; Mitochondria
PubMed: 38036728
DOI: 10.1038/s12276-023-01121-x -
Journal of Translational Medicine Oct 2023Copper (Cu) is an essential element that is involved in a variety of biochemical processes. Both deficiency and accumulation of Cu are associated with various diseases;... (Review)
Review
Copper (Cu) is an essential element that is involved in a variety of biochemical processes. Both deficiency and accumulation of Cu are associated with various diseases; and a high amount of accumulated Cu in cells can be fatal. The production of reactive oxygen species (ROS), oxidative stress, and cuproptosis are among the proposed mechanisms of copper toxicity at high concentrations. Elesclomol (ELC) is a mitochondrion-targeting agent discovered for the treatment of solid tumors. In this review, we summarize the synthesis of this drug, its mechanisms of action, and the current status of its applications in the treatment of various diseases such as cancer, tuberculosis, SARS-CoV-2 infection, and other copper-associated disorders. We also provide some detailed information about future directions to improve its clinical performance.
Topics: Humans; Copper; Antineoplastic Agents; Oxidative Stress; Neoplasms; Mitochondria
PubMed: 37864163
DOI: 10.1186/s12967-023-04533-5 -
Frontiers in Bioscience (Landmark... Sep 2023Prohibitin-2 (PHB2) is a conserved protein in mitochondria that regulates various biological processes, including cell cycle, proliferation, apoptosis, transcription,... (Review)
Review
Prohibitin-2 (PHB2) is a conserved protein in mitochondria that regulates various biological processes, including cell cycle, proliferation, apoptosis, transcription, signal transduction, and mitochondrial ridge morphogenesis. Recently, there has been growing interest in the biological function of PHB2. This article primarily discusses the recent advances in the role of PHB2 in diseases.
Topics: Prohibitins; Mitochondria; Signal Transduction
PubMed: 37796696
DOI: 10.31083/j.fbl2809211 -
Cells May 2023The mitochondrion has a unique position among other cellular organelles due to its dynamic properties and symbiotic nature, which is reflected in an active exchange of... (Review)
Review
The mitochondrion has a unique position among other cellular organelles due to its dynamic properties and symbiotic nature, which is reflected in an active exchange of metabolites and cofactors between the rest of the intracellular compartments. The mitochondrial energy metabolism is greatly dependent on nicotinamide adenine dinucleotide (NAD) as a cofactor that is essential for both the activity of respiratory and TCA cycle enzymes. The NAD level is determined by the rate of NAD synthesis, the activity of NAD-consuming enzymes, and the exchange rate between the individual subcellular compartments. In this review, we discuss the NAD synthesis pathways, the NAD degradation enzymes, and NAD subcellular localization, as well as NAD transport mechanisms with a focus on mitochondria. Finally, the effect of the pathologic depletion of mitochondrial NAD pools on mitochondrial proteins' post-translational modifications and its role in neurodegeneration will be reviewed. Understanding the physiological constraints and mechanisms of NAD maintenance and the exchange between subcellular compartments is critical given NAD's broad effects and roles in health and disease.
Topics: NAD; Mitochondria; Homeostasis; Organelles; Energy Metabolism
PubMed: 37174729
DOI: 10.3390/cells12091329 -
Cellular and Molecular Life Sciences :... Aug 2023Lipids in cell membranes and subcellular compartments play essential roles in numerous cellular processes, such as energy production, cell signaling and inflammation. A... (Review)
Review
Lipids in cell membranes and subcellular compartments play essential roles in numerous cellular processes, such as energy production, cell signaling and inflammation. A specific organelle lipidome is characterized by lipid synthesis and metabolism, intracellular trafficking, and lipid homeostasis in the organelle. Over the years, considerable effort has been directed to the identification of the lipid fingerprints of cellular organelles. However, these fingerprints are not fully characterized due to the large variety and structural complexity of lipids and the great variability in the abundance of different lipid species. The process becomes even more challenging when considering that the lipidome differs in health and disease contexts. This review summarizes the information available on the lipid composition of mammalian cell organelles, particularly the lipidome of the nucleus, mitochondrion, endoplasmic reticulum, Golgi apparatus, plasma membrane and organelles in the endocytic pathway. The lipid compositions of extracellular vesicles and lamellar bodies are also described. In addition, several examples of subcellular lipidome dynamics under physiological and pathological conditions are presented. Finally, challenges in mapping organelle lipidomes are discussed.
Topics: Animals; Lipids; Lipidomics; Lipid Metabolism; Organelles; Cell Nucleus; Mitochondria; Mammals
PubMed: 37530856
DOI: 10.1007/s00018-023-04889-3 -
Neural Plasticity 2020Sensorineural hearing loss (SNHL) becomes an inevitable worldwide public health issue, and deafness treatment is urgently imperative; yet their current curative therapy... (Review)
Review
Sensorineural hearing loss (SNHL) becomes an inevitable worldwide public health issue, and deafness treatment is urgently imperative; yet their current curative therapy is limited. Auditory neuropathies (AN) were proved to play a substantial role in SNHL recently, and spiral ganglion neuron (SGN) dysfunction is a dominant pathogenesis of AN. Auditory pathway is a high energy consumption system, and SGNs required sufficient mitochondria. Mitochondria are known treatment target of SNHL, but mitochondrion mechanism and pathology in SGNs are not valued. Mitochondrial dysfunction and pharmacological therapy were studied in neurodegeneration, providing new insights in mitochondrion-targeted treatment of AN. In this review, we summarized mitochondrial biological functions related to SGNs and discussed interaction between mitochondrial dysfunction and AN, as well as existing mitochondrion treatment for SNHL. Pharmaceutical exploration to protect mitochondrion dysfunction is a feasible and effective therapeutics for AN.
Topics: Animals; Auditory Pathways; Hearing Loss, Central; Humans; Mice; Mitochondria; Neurons; Spiral Ganglion
PubMed: 32908487
DOI: 10.1155/2020/8843485