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The Journal of Physiology Feb 2021Mitochondrial health is an important mediator of cellular function across a range of tissues, and as a result contributes to whole-body vitality in health and disease.... (Review)
Review
Mitochondrial health is an important mediator of cellular function across a range of tissues, and as a result contributes to whole-body vitality in health and disease. Our understanding of the regulation and function of these organelles is of great interest to scientists and clinicians across many disciplines within our healthcare system. Skeletal muscle is a useful model tissue for the study of mitochondrial adaptations because of its mass and contribution to whole body metabolism. The remarkable plasticity of mitochondria allows them to adjust their volume, structure and capacity under conditions such as exercise, which is useful or improving metabolic health in individuals with various diseases and/or advancing age. Mitochondria exist within muscle as a functional reticulum which is maintained by dynamic processes of biogenesis and fusion, and is balanced by opposing processes of fission and mitophagy. The sophisticated coordination of these events is incompletely understood, but is imperative for organelle function and essential for the maintenance of an interconnected organelle network that is finely tuned to the metabolic needs of the cell. Further elucidation of the mechanisms of mitochondrial turnover in muscle could offer potential therapeutic targets for the advancement of health and longevity among our ageing populations. As well, investigating exercise modalities that are both convenient and capable of inducing robust mitochondrial adaptations are useful in fostering more widespread global adherence. To this point, exercise remains the most potent behavioural therapeutic approach for the improvement of mitochondrial health, not only in muscle, but potentially also in other tissues.
Topics: Exercise; Humans; Mitochondria; Mitochondria, Muscle; Mitophagy; Muscle, Skeletal; Organelle Biogenesis
PubMed: 31674658
DOI: 10.1113/JP278853 -
The FEBS Journal Nov 2022The migrasome is a newly discovered organelle produced by migrating cells. As cells migrate, long and thin retraction fibers are left in their wake. On these fibers, we... (Review)
Review
The migrasome is a newly discovered organelle produced by migrating cells. As cells migrate, long and thin retraction fibers are left in their wake. On these fibers, we discovered the production of a pomegranate-like structure, which we named migrasomes. The production of migrasomes is highly correlated with the migration of cells. Currently, it has been demonstrated the migrasomes exhibit three modes of action: release of signaling molecules through rupturing or leaking, carriers of damaged mitochondria, and lateral transfer of mRNA or proteins. In this review, we would like to discuss, in detail, the functions, mechanisms, and potential applications of this newly discovered cell organelle.
Topics: Cell Movement; Organelles; Mitochondria; Signal Transduction; Organelle Biogenesis
PubMed: 34492154
DOI: 10.1111/febs.16183 -
Methods in Cell Biology 2020Isolated mitochondria are useful to study fundamental processes including mitochondrial respiration, metabolic activity, protein import, membrane fusion, protein complex...
Isolated mitochondria are useful to study fundamental processes including mitochondrial respiration, metabolic activity, protein import, membrane fusion, protein complex assembly, as well as interactions of mitochondria with the cytoskeleton, nuclear encoded mRNAs, and other organelles. In addition, studies of the mitochondrial proteome, phosphoproteome, and lipidome are dependent on preparation of highly purified mitochondria (Boldogh, Vojtov, Karmon, & Pon, 1998; Cui, Conte, Fox, Zara, & Winge, 2014; Marc et al., 2002; Meeusen, McCaffery, & Nunnari, 2004; Reinders et al., 2007; Schneiter et al., 1999; Stuart & Koehler, 2007). Most methods to isolate mitochondria rely on differential centrifugation, a two-step centrifugation carried out at low speed to remove intact cells, cell and tissue debris, and nuclei from whole cell extracts followed by high speed centrifugation to concentrate mitochondria and separate them from other organelles. However, methods to disrupt cells and tissue vary. Moreover, density gradient centrifugation or affinity purification of the organelle are used to further purify mitochondria or to separate different populations of the organelle. Here, we describe protocols to isolate mitochondria from different cells and tissues as well as approaches to assess the purity and integrity of isolated organelles.
Topics: Animals; Brain; Cell Fractionation; Cells, Cultured; Centrifugation, Density Gradient; Mitochondria; Mitochondria, Heart; Mitochondria, Liver; Mitochondria, Muscle; Organ Specificity; Rats; Saccharomyces cerevisiae
PubMed: 32183964
DOI: 10.1016/bs.mcb.2019.10.002 -
Autophagy Feb 2021The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is... (Review)
Review
The structural integrity and functional stability of organelles are prerequisites for the viability and responsiveness of cells. Dysfunction of multiple organelles is critically involved in the pathogenesis and progression of various diseases, such as chronic obstructive pulmonary disease, cardiovascular diseases, infection, and neurodegenerative diseases. In fact, those organelles synchronously present with evident structural derangement and aberrant function under exposure to different stimuli, which might accelerate the corruption of cells. Therefore, the quality control of multiple organelles is of great importance in maintaining the survival and function of cells and could be a potential therapeutic target for human diseases. Organelle-specific autophagy is one of the major subtypes of autophagy, selectively targeting different organelles for quality control. This type of autophagy includes mitophagy, pexophagy, reticulophagy (endoplasmic reticulum), ribophagy, lysophagy, and nucleophagy. These kinds of organelle-specific autophagy are reported to be beneficial for inflammatory disorders by eliminating damaged organelles and maintaining homeostasis. In this review, we summarized the recent findings and mechanisms covering different kinds of organelle-specific autophagy, as well as their involvement in various diseases, aiming to arouse concern about the significance of the quality control of multiple organelles in the treatment of inflammatory diseases. ABCD3: ATP binding cassette subfamily D member 3; AD: Alzheimer disease; ALS: amyotrophic lateral sclerosis; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; ARIH1: ariadne RBR E3 ubiquitin protein ligase 1; ATF: activating transcription factor; ATG: autophagy related; ATM: ATM serine/threonine kinase; BCL2: BCL2 apoptosis regulator; BCL2L11/BIM: BCL2 like 11; BCL2L13: BCL2 like 13; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; BNIP3L/NIX: BCL2 interacting protein 3 like; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CANX: calnexin; CAT: catalase; CCPG1: cell cycle progression 1; CHDH: choline dehydrogenase; COPD: chronic obstructive pulmonary disease; CSE: cigarette smoke exposure; CTSD: cathepsin D; DDIT3/CHOP: DNA-damage inducible transcript 3; DISC1: DISC1 scaffold protein; DNM1L/DRP1: dynamin 1 like; EIF2AK3/PERK: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2S1/eIF2α: eukaryotic translation initiation factor 2 alpha kinase 3; EMD: emerin; EPAS1/HIF-2α: endothelial PAS domain protein 1; ER: endoplasmic reticulum; ERAD: ER-associated degradation; ERN1/IRE1α: endoplasmic reticulum to nucleus signaling 1; FBXO27: F-box protein 27; FKBP8: FKBP prolyl isomerase 8; FTD: frontotemporal dementia; FUNDC1: FUN14 domain containing 1; G3BP1: G3BP stress granule assembly factor 1; GBA: glucocerebrosidase beta; HIF1A/HIF1: hypoxia inducible factor 1 subunit alpha; IMM: inner mitochondrial membrane; LCLAT1/ALCAT1: lysocardiolipin acyltransferase 1; LGALS3/Gal3: galectin 3; LIR: LC3-interacting region; LMNA: lamin A/C; LMNB1: lamin B1; LPS: lipopolysaccharide; MAPK8/JNK: mitogen-activated protein kinase 8; MAMs: mitochondria-associated membranes; MAP1LC3B/LC3B: microtubule-associated protein 1 light chain 3 beta; MFN1: mitofusin 1; MOD: multiple organelles dysfunction; MTPAP: mitochondrial poly(A) polymerase; MUL1: mitochondrial E3 ubiquitin protein ligase 1; NBR1: NBR1 autophagy cargo receptor; NLRP3: NLR family pyrin domain containing 3; NUFIP1: nuclear FMR1 interacting protein 1; OMM: outer mitochondrial membrane; OPTN: optineurin; PD: Parkinson disease; PARL: presenilin associated rhomboid like; PEX3: peroxisomal biogenesis factor 3; PGAM5: PGAM family member 5; PHB2: prohibitin 2; PINK1: PTEN induced putative kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RB1CC1/FIP200: RB1 inducible coiled-coil 1; RETREG1/FAM134B: reticulophagy regulator 1; RHOT1/MIRO1: ras homolog family member T1; RIPK3/RIP3: receptor interacting serine/threonine kinase 3; ROS: reactive oxygen species; RTN3: reticulon 3; SEC62: SEC62 homolog, preprotein translocation factor; SESN2: sestrin2; SIAH1: siah E3 ubiquitin protein ligase 1; SNCA: synuclein alpha; SNCAIP: synuclein alpha interacting protein; SQSTM1/p62: sequestosome 1; STING1: stimulator of interferon response cGAMP interactor 1; TAX1BP1: Tax1 binding protein 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; TICAM1/TRIF: toll-like receptor adaptor molecule 1; TIMM23: translocase of inner mitochondrial membrane 23; TNKS: tankyrase; TOMM: translocase of the outer mitochondrial membrane; TRIM: tripartite motif containing; UCP2: uncoupling protein 2; ULK1: unc-51 like autophagy activating kinase; UPR: unfolded protein response; USP10: ubiquitin specific peptidase 10; VCP/p97: valosin containing protein; VDAC: voltage dependent anion channels; XIAP: X-linked inhibitor of apoptosis; ZNHIT3: zinc finger HIT-type containing 3.
Topics: Autophagy; Endoribonucleases; Humans; Inflammation; Mitophagy; Organelles; Prohibitins; Quality Control
PubMed: 32048886
DOI: 10.1080/15548627.2020.1725377 -
EMBO Reports Aug 2022Eukaryotic cells adequately control the mass and functions of organelles in various situations. Autophagy, an intracellular degradation system, largely contributes to... (Review)
Review
Eukaryotic cells adequately control the mass and functions of organelles in various situations. Autophagy, an intracellular degradation system, largely contributes to this organelle control by degrading the excess or defective portions of organelles. The endoplasmic reticulum (ER) is an organelle with distinct structural domains associated with specific functions. The ER dynamically changes its mass, components, and shape in response to metabolic, developmental, or proteotoxic cues to maintain or regulate its functions. Therefore, elaborate mechanisms are required for proper degradation of the ER. Here, we review our current knowledge on diverse mechanisms underlying selective autophagy of the ER, which enable efficient degradation of specific ER subdomains according to different demands of cells.
Topics: Autophagy; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Macroautophagy
PubMed: 35758175
DOI: 10.15252/embr.202255192 -
The Journal of Cell Biology Oct 2022The endoplasmic reticulum (ER), which occupies a large portion of the cytoplasm, is the cell's main site for the biosynthesis of lipids and carbohydrate conjugates, and... (Review)
Review
The endoplasmic reticulum (ER), which occupies a large portion of the cytoplasm, is the cell's main site for the biosynthesis of lipids and carbohydrate conjugates, and it is essential for folding, assembly, and biosynthetic transport of secreted proteins and integral membrane proteins. The discovery of abundant membrane contact sites (MCSs) between the ER and other membrane compartments has revealed that, in addition to its biosynthetic and secretory functions, the ER plays key roles in the regulation of organelle dynamics and functions. In this review, we will discuss how the ER regulates endosomes, lysosomes, autophagosomes, mitochondria, peroxisomes, and the Golgi apparatus via MCSs. Such regulation occurs via lipid and Ca2+ transfer and also via control of in trans dephosphorylation reactions and organelle motility, positioning, fusion, and fission. The diverse controls of other organelles via MCSs manifest the ER as master regulator of organelle biology.
Topics: Calcium; Carbohydrates; Cell Membrane; Endoplasmic Reticulum; Lipids; Membrane Proteins; Organelles
PubMed: 36108241
DOI: 10.1083/jcb.202205135 -
Trends in Neurosciences Apr 2022Neurons rely heavily on properly regulated mitochondrial and lysosomal homeostasis, with multiple neurodegenerative diseases linked to dysfunction in these two... (Review)
Review
Neurons rely heavily on properly regulated mitochondrial and lysosomal homeostasis, with multiple neurodegenerative diseases linked to dysfunction in these two organelles. Interestingly, mitochondria-lysosome membrane contact sites have been identified as a key pathway mediating their crosstalk in neurons. Recent studies have further elucidated the regulation of mitochondria-lysosome contact dynamics via distinct tethering/untethering protein machinery. Moreover, this pathway has been shown to have additional functions in regulating organelle network dynamics and metabolite transfer between lysosomes and mitochondria. In this review, we highlight recent advances in the field of mitochondria-lysosome contact sites and their misregulation across multiple neurodegenerative disorders, which further underscore a potential role for this pathway in neuronal homeostasis and disease.
Topics: Humans; Intracellular Membranes; Lysosomes; Mitochondria; Neurodegenerative Diseases; Neurons
PubMed: 35249745
DOI: 10.1016/j.tins.2022.01.005 -
The Journal of Cell Biology Dec 2020Diverse pathogen- and damage-associated stresses drive inflammation via activation of the multimolecular NLRP3-inflammasome complex. How the effects of diverse stimuli... (Review)
Review
Diverse pathogen- and damage-associated stresses drive inflammation via activation of the multimolecular NLRP3-inflammasome complex. How the effects of diverse stimuli are integrated by the cell to regulate NLRP3 has been the subject of intense research, and yet an accepted unifying hypothesis for the control of NLRP3 remains elusive. Here, we review the literature on the effects of NLRP3-activating stimuli on subcellular organelles and conclude that a shared feature of NLRP3-activating stresses is an organelle dysfunction. In particular, we propose that the endosome may be more important than previously recognized as a signal-integrating hub for NLRP3 activation in response to many stimuli and may also link to the dysfunction of other organelles. In addition, NLRP3-inflammasome-activating stimuli trigger diverse posttranslational modifications of NLRP3 that are important in controlling its activation. Future research should focus on how organelles respond to specific NLRP3-activating stimuli, and how this relates to posttranslational modifications, to delineate the organellar control of NLRP3.
Topics: Animals; Humans; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Organelles; Protein Processing, Post-Translational; Signal Transduction; Stress, Physiological
PubMed: 33044555
DOI: 10.1083/jcb.202006194 -
Trends in Neurosciences Feb 2023Efforts to understand how mitochondrial dysfunction contributes to neurodegeneration have primarily focussed on the role of mitochondria in neuronal energy metabolism.... (Review)
Review
Efforts to understand how mitochondrial dysfunction contributes to neurodegeneration have primarily focussed on the role of mitochondria in neuronal energy metabolism. However, progress in understanding the etiological nature of emerging mitochondrial functions has yielded new ideas about the mitochondrial basis of neurological disease. Studies aimed at deciphering how mitochondria signal through interorganellar contacts, vesicular trafficking, and metabolic transmission have revealed that mitochondrial regulation of immunometabolism, cell death, organelle dynamics, and neuroimmune interplay are critical determinants of neural health. Moreover, the homeostatic mechanisms that exist to protect mitochondrial health through turnover via nanoscale proteostasis and lysosomal degradation have become integrated within mitochondrial signalling pathways to support metabolic plasticity and stress responses in the nervous system. This review highlights how these distinct mitochondrial pathways converge to influence neurological health and contribute to disease pathology.
Topics: Humans; Mitochondria; Organelles; Homeostasis; Signal Transduction; Nervous System Diseases
PubMed: 36635110
DOI: 10.1016/j.tins.2022.12.001 -
The Yale Journal of Biology and Medicine Sep 2019Lipid droplets are cytosolic fat storage organelles present in most eukaryotic cells. Long regarded merely as inert fat reservoirs, they are now emerging as major... (Review)
Review
Lipid droplets are cytosolic fat storage organelles present in most eukaryotic cells. Long regarded merely as inert fat reservoirs, they are now emerging as major regulators of cellular metabolism. They act as hubs that coordinate the pathways of lipid uptake, distribution, storage, and use in the cell. Recent studies have revealed that they are also essential components of the cellular stress response. One of the hallmark characteristics of lipid droplets is their capacity to buffer excess lipids and to finely tune their subsequent release based on specific cellular requirements. This simple feature of lipid droplet biology, buffering and delayed release of lipids, forms the basis for their pleiotropic roles in the cellular stress response. In stressed cells, lipid droplets maintain energy and redox homeostasis and protect against lipotoxicity by sequestering toxic lipids into their neutral lipid core. Their mobility and dynamic interactions with mitochondria enable an efficient delivery of fatty acids for optimal energy production. Lipid droplets are also involved in the maintenance of membrane and organelle homeostasis by regulating membrane composition, preventing lipid peroxidation and removing damaged proteins and lipids. Finally, they also engage in a symbiotic relationship with autophagy and act as reservoirs of bioactive lipids that regulate inflammation and immunity. Thus, lipid droplets are central managers of lipid metabolism that function as safeguards against various types of cellular stress.
Topics: Animals; Energy Metabolism; Homeostasis; Humans; Lipid Droplets; Lipids; Organelles; Stress, Physiological
PubMed: 31543707
DOI: No ID Found