Loss of PINK1 function promotes mitophagy through effects on oxidative stress and mitochondrial fission.
AuthorsDagda RK, Cherra SJ, Kulich SM, Tandon A, Park D, Chu CT,
JournalJ Biol Chem
PubMed ID19279012
'Mitochondrial dysregulation is strongly implicated in Parkinson disease. Mutations in PTEN-induced kinase 1 (PINK1) are associated with familial parkinsonism and neuropsychiatric disorders. Although overexpressed PINK1 is neuroprotective, less is known about neuronal responses to loss of PINK1 function. We found that stable knockdown of PINK1 induced mitochondrial fragmentation and autophagy ... More
Flow cytometric determination of mitochondrial membrane potential changes during apoptosis of T lymphocytic and pancreatic beta cell lines: comparison of tetramethylrhodamineethylester (TMRE), chloromethyl-X-rosamine (H2-CMX-Ros) and MitoTracker Red 580 (MTR580).
AuthorsJayaraman S
JournalJ Immunol Methods
PubMed ID16256133
'The mitochondria-specific dyes, TMRE, H2-CMX-Ros and MTR580 were determined for their suitability to measure mitochondrial potential changes of the T cell leukemia cell line Jurkat and insulin-secreting beta cell line NIT-1 during apoptosis. Both freshly harvested Jurkat and NIT-1 cells induced to undergo apoptosis displayed poor retention of the potential-sensitive, ... More
Three novel Bid proteins generated by alternative splicing of the human Bid gene.
'Bid, a BH3-only Bcl-2 protein, is activated by proteolytic cleavage exposing the BH3 domain, which then induces apoptosis by interacting with pro-apoptotic Bcl-2 family proteins (e.g. Bax and Bak) at the mitochondrial surface. The arrangement of domains within Bid suggested that Bid function might be regulated in part by alternative ... More
Ketamine induces toxicity in human neurons differentiated from embryonic stem cells via mitochondrial apoptosis pathway.
AuthorsBosnjak ZJ, Yan Y, Canfield S, Muravyeva MY, Kikuchi C, Wells CW, Corbett JA, Bai X,
JournalCurr Drug Saf
PubMed ID22873495
'Ketamine is widely used for anesthesia in pediatric patients. Growing evidence indicates that ketamine causes neurotoxicity in a variety of developing animal models. Our understanding of anesthesia neurotoxicity in humans is currently limited by difficulties in obtaining neurons and performing developmental toxicity studies in fetal and pediatric populations. It may ... More
Novel guanidine-containing molecular transporters based on lactose scaffolds: lipophilicity effect on the intracellular organellar selectivity.
AuthorsBiswas G, Jeon OY, Lee WS, Kim DC, Kim KT, Lee S, Chang S, Chung SK,
JournalChemistry
PubMed ID18770513
We have synthesized two lactose-based molecular transporters, each containing seven guanidine residues attached to the lactose scaffold through omega-aminocarboxylate linker chains of two different lengths, and have examined their cellular uptakes and intracellular and organellar localizations in HeLa cells, as well as their tissue distributions in mice. Both molecular transporters ... More
A lethal defect of mitochondrial and peroxisomal fission.
AuthorsWaterham HR, Koster J, van Roermund CW, Mooyer PA, Wanders RJ, Leonard JV
JournalN Engl J Med
PubMed ID17460227
We report on a newborn girl with microcephaly, abnormal brain development, optic atrophy and hypoplasia, persistent lactic acidemia, and a mildly elevated plasma concentration of very-long-chain fatty acids. We found a defect of the fission of both mitochondria and peroxisomes, as well as a heterozygous, dominant-negative mutation in the dynamin-like ... More
Antibody-targeted nanovectors for the treatment of brain cancers.
AuthorsSharpe MA, Marcano DC, Berlin JM, Widmayer MA, Baskin DS, Tour JM,
JournalACS Nano
PubMed ID22390360
Introduced here is the hydrophilic carbon clusters (HCCs) antibody drug enhancement system (HADES), a methodology for cell-specific drug delivery. Antigen-targeted, drug-delivering nanovectors are manufactured by combining specific antibodies with drug-loaded poly(ethylene glycol)-HCCs (PEG-HCCs). We show that HADES is highly modular, as both the drug and antibody component can be varied ... More
Monitoring autophagy in lysosomal storage disorders.
AuthorsRaben N, Shea L, Hill V, Plotz P,
JournalMethods Enzymol
PubMed ID19216919
Lysosomes are the final destination of the autophagic pathway. It is in the acidic milieu of the lysosomes that autophagic cargo is metabolized and recycled. One would expect that diseases with primary lysosomal defects would be among the first systems in which autophagy would be studied. In reality, this is ... More
Mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of spinocerebellar ataxia type 12 (SCA12).
AuthorsWang YC, Lee CM, Lee LC, Tung LC, Hsieh-Li HM, Lee-Chen GJ, Su MT,
JournalJ Biol Chem
PubMed ID21471219
Spinal cerebellar ataxia type 12 (SCA12) has been attributed to the elevated expression of ppp2r2b. To better elucidate the pathomechanism of the neuronal disorder and to search for a pharmacological treatment, Drosophila models of SCA12 were generated by overexpression of a human ppp2r2b and its Drosophila homolog tws. Ectopic expression ... More
Re-organization of mitochondria at the NK cell immune synapse.
AuthorsAbarca-Rojano E, Muñiz-Hernández S, Moreno-Altamirano MM, Mondragón-Flores R, Enriquez-Rincón F, Sánchez-García FJ,
JournalImmunol Lett
PubMed ID19038287
As part of the innate immune response NK cells destroy infected, transformed, or otherwise stressed cells within hours of activation. In contrast, CD4(+) T lymphocytes require a sustained increase in their metabolism in order to cope with the biogenesis of cell components, in a process of proliferation and differentiation into ... More
Stable synthetic bacteriochlorins overcome the resistance of melanoma to photodynamic therapy.
AuthorsMroz P, Huang YY, Szokalska A, Zhiyentayev T, Janjua S, Nifli AP, Sherwood ME, Ruzié C, Borbas KE, Fan D, Krayer M, Balasubramanian T, Yang E, Kee HL, Kirmaier C, Diers JR, Bocian DF, Holten D, Lindsey JS, Hamblin MR,
JournalFASEB J
PubMed ID20385618
Cutaneous malignant melanoma remains a therapeutic challenge, and patients with advanced disease have limited survival. Photodynamic therapy (PDT) has been successfully used to treat many malignancies, and it may show promise as an antimelanoma modality. However, high melanin levels in melanomas can adversely affect PDT effectiveness. Herein the extent of ... More
Chelation of lysosomal iron protects dopaminergic SH-SY5Y neuroblastoma cells from hydrogen peroxide toxicity by precluding autophagy and Akt dephosphorylation.
AuthorsCastino R, Fiorentino I, Cagnin M, Giovia A, Isidoro C,
JournalToxicol Sci
PubMed ID21742779
In human neuroblastoma SH-SY5Y cells, hydrogen peroxide (H(2)O(2), 200µM) rapidly (< 5 min) induced autophagy, as shown by processing and vacuolar relocation of light chain 3(LC3). Accumulation of autophagosome peaked at 30 min of H(2)O(2) exposure. The continuous presence of H(2)O(2) eventually (at > 60 min) caused autophagy-dependent annexin V-positive ... More
Autophagy in neurite injury and neurodegeneration: in vitro and in vivo models.
Recent advances indicate that maintaining a balanced level of autophagy is critically important for neuronal health and function. Pathologic dysregulation of macroautophagy has been implicated in synaptic dysfunction, cellular stress, and neuronal cell death. Autophagosomes and autolysosomes are induced in acute and chronic neurological disorders including stroke, brain trauma, neurotoxin ... More
Amyloid-beta overproduction causes abnormal mitochondrial dynamics via differential modulation of mitochondrial fission/fusion proteins.
AuthorsWang X, Su B, Siedlak SL, Moreira PI, Fujioka H, Wang Y, Casadesus G, Zhu X,
JournalProc Natl Acad Sci U S A
PubMed ID19050078
Mitochondrial dysfunction is a prominent feature of Alzheimer disease but the underlying mechanism is unclear. In this study, we investigated the effect of amyloid precursor protein (APP) and amyloid beta on mitochondrial dynamics in neurons. Confocal and electron microscopic analysis demonstrated that approximately 40% M17 cells overexpressing WT APP (APPwt ... More
Mitochondrially localized ERK2 regulates mitophagy and autophagic cell stress: implications for Parkinson's disease.
AuthorsDagda RK, Zhu J, Kulich SM, Chu CT,
JournalAutophagy
PubMed ID18594198
Degenerating neurons of Parkinson's disease (PD) patient brains exhibit granules of phosphorylated extracellular signal-regulated protein kinase 1/2 (ERK1/2) that localize to autophagocytosed mitochondria. Here we show that 6-hydroxydopamine (6-OHDA) elicits activity-related localization of ERK1/2 in mitochondria of SH-SY5Y cells, and these events coincide with induction of autophagy and precede mitochondrial ... More
Accessibility of nuclear chromatin by DNA binding polyamides.
Pyrrole-imidazole polyamides bind DNA with affinities comparable to those of transcriptional regulatory proteins and inhibit the DNA binding activities of components of the transcription apparatus. If polyamides are to be useful for the regulation of gene expression in cell culture experiments, one pivotal issue is accessibility of specific sites in ... More
Coupling of caspase-9 to Apaf1 in response to loss of pRb or cytotoxic drugs is cell-type-specific.
AuthorsHo AT, Li QH, Hakem R, Mak TW, Zacksenhaus E
JournalEMBO J
PubMed ID14713951
Inactivation of the tumor suppressor Rb in the mouse induces cell death, which depends entirely (in lens, CNS) and only partly (PNS, skeletal muscles) on Apaf1/Ced4, an apoptosomal factor thought to be required for processing procaspase-9 following mitochondrial permeabilization. Here, we report that in response to cytotoxic drugs, Apaf1(-/-) primary ... More
Properties of phosphoenolpyruvate mutase, the first enzyme in the aminoethylphosphonate biosynthetic pathway in Trypanosoma cruzi.
AuthorsSarkar M, Hamilton CJ, Fairlamb AH
JournalJ Biol Chem
PubMed ID12672809
Phosphoenolpyruvate (PEP) mutase catalyzes the conversion of phosphoenolpyruvate to phosphonopyruvate, the initial step in the formation of many naturally occurring phosphonate compounds. The phosphonate compound 2-aminoethylphosphonate is present as a component of complex carbohydrates on the surface membrane of many trypanosomatids including glycosylinositolphospholipids of Trypanosoma cruzi. Using partial sequence information ... More
The T cell receptor gamma chain alternate reading frame protein (TARP), a prostate-specific protein localized in mitochondria.
AuthorsMaeda H, Nagata S, Wolfgang CD, Bratthauer GL, Bera TK, Pastan I
JournalJ Biol Chem
PubMed ID15150260
We previously showed that mRNA encoding TARP (T cell receptor gamma chain alternate reading frame protein) is exclusively expressed in the prostate in males and is up-regulated by androgen in LNCaP cells, an androgen-sensitive prostate cancer cell line. We have now developed an anti-TARP monoclonal antibody named TP1, and show ... More
Asbestos-induced apoptosis is protein kinase C delta-dependent.
AuthorsShukla A, Stern M, Lounsbury KM, Flanders T, Mossman BT
JournalAm J Respir Cell Mol Biol
PubMed ID12626342
Alveolar epithelial and mesothelial cells undergo apoptosis in response to asbestos, a phenomenon that may be important in injury and/or initiation of compensatory proliferation. Here, we report a functional role of protein kinase (PKC)delta in apoptosis by crocidolite asbestos. We first show that asbestos increases the kinase activity of PKC ... More
Distinct domains for anti- and pro-apoptotic activities of IEX-1.
AuthorsShen L, Guo J, Santos-Berrios C, Wu MX
JournalJ Biol Chem
PubMed ID16567805
IEX-1 (immediate early response gene X-1) is a stress-inducible gene. Its overexpression can suppress or enhance apoptosis dependent on the nature of stress, yet the polypeptide does not possess any of the functional domains that are homologous to those present in well characterized effectors or inhibitors of apoptosis. This study ... More
Brain oxidation is an initial process in sleep induction.
AuthorsIkeda M, Ikeda-Sagara M, Okada T, Clement P, Urade Y, Nagai T, Sugiyama T, Yoshioka T, Honda K, Inoué S
JournalNeuroscience
PubMed ID15652998
CNS activity is generally coupled to the vigilance state, being primarily active during wakefulness and primarily inactive during deep sleep. During periods of high neuronal activity, a significant volume of oxygen is used to maintain neuronal membrane potentials, which subsequently produces cytotoxic reactive oxygen species (ROS). Glutathione, a major endogenous ... More
Hypothyroid phenotype is contributed by mitochondrial complex I inactivation due to translocated neuronal nitric-oxide synthase.
Although transcriptional effects of thyroid hormones have substantial influence on oxidative metabolism, how thyroid sets basal metabolic rate remains obscure. Compartmental localization of nitric-oxide synthases is important for nitric oxide signaling. We therefore examined liver neuronal nitric-oxide synthase-alpha (nNOS) subcellular distribution as a putative mechanism for thyroid effects on rat ... More
Induction of mitochondrial fusion by cysteine-alkylators ethacrynic acid and N-ethylmaleimide.
AuthorsBowes TJ, Gupta RS
JournalJ Cell Physiol
PubMed ID15389563
Mitochondrial fusion and fission are important aspects of eukaryotic cell function that permit the adoption of varied mitochondrial morphologies depending upon cellular physiology. We previously observed that ethacrynic acid (EA) induced mitochondrial fusion in cultured BSC-1 and CHO/wt cells. However, the mechanism responsible for it was not clear since EA ... More
The HIV-1 nucleoside reverse transcriptase inhibitors stavudine and zidovudine alter adipocyte functions in vitro.
AuthorsCaron M, Auclair M, Lagathu C, Lombès A, Walker UA, Kornprobst M, Capeau J
JournalAIDS
PubMed ID15577645
OBJECTIVES: Nucleoside analogues are suspected of playing a role in peripheral fat loss in patients during long-term treatment with antiretroviral drugs. DESIGN AND METHODS: We compared the long-term effects of stavudine (10 microM), zidovudine (1 muM), didanosine (10 microM), abacavir (4 microM), lamivudine (10 microM), and tenofovir (1 microM), near ... More
Chronology of cellular events related to mitochondrial burnout leading to cell death in Fuchs endothelial corneal dystrophy.
AuthorsMéthot SJ, Proulx S, Brunette I, Rochette PJ
JournalSci Rep
PubMed ID32242036
'Fuchs endothelial corneal dystrophy (FECD) is a degenerative eye disease characterized by corneal endothelial cell (CEC) death and the formation of guttae, an abnormal thickening of CEC''s basement membrane. At the tissue level, an oxidative stress causing mitochondrial damage and CEC death have been described to explain FECD pathogenesis. At ... More
Verteporfin inhibits oxidative phosphorylation and induces cell death specifically in glioma stem cells.
AuthorsKuramoto K, Yamamoto M, Suzuki S, Sanomachi T, Togashi K, Seino S, Kitanaka C, Okada M
JournalFEBS J
PubMed ID31868973
'Glioblastoma multiforme (GBM) is the most malignant primary brain tumour in adults. Since glioma stem cells (GSCs) are associated with therapeutic resistance as well as the initiation and recurrence in GBM, therapies targeting GSCs are considered to be effective for long-term survival in GBM. Several reports suggested that oxidative phosphorylation ... More
Phase separation of Nur77 mediates celastrol-induced mitophagy by promoting the liquidity of p62/SQSTM1 condensates.
Authors
JournalNat Commun
PubMed ID34645818
PHD3 Loss Promotes Exercise Capacity and Fat Oxidation in Skeletal Muscle.
Authors
JournalCell Metab
PubMed ID32663458
All-Optical Wide-Field Selective Imaging of Fluorescent Nanodiamonds in Cells, In Vivo and Ex Vivo.
Authors
JournalACS Nano
PubMed ID34339180
3D Correlative Cryo-Structured Illumination Fluorescence and Soft X-ray Microscopy Elucidates Reovirus Intracellular Release Pathway.
Authors
JournalCell
PubMed ID32610083
Paradoxical Mitophagy Regulation by PINK1 and TUFm.
Authors
JournalMol Cell
PubMed ID33113344
Distinct fission signatures predict mitochondrial degradation or biogenesis.
Authors
JournalNature
PubMed ID33953403
Visualizing and Modulating Mitophagy for Therapeutic Studies of Neurodegeneration.
Authors
JournalCell
PubMed ID32437660
4D analysis of malaria parasite invasion offers insights into erythrocyte membrane remodeling and parasitophorous vacuole formation.
Authors
JournalNat Commun
PubMed ID34131147
Neutralization of Oxidized Phospholipids Ameliorates Non-alcoholic Steatohepatitis.
Authors
JournalCell Metab
PubMed ID31761566
Targeting DGAT1 Ameliorates Glioblastoma by Increasing Fat Catabolism and Oxidative Stress.
AuthorsZhang J, Fan J, Li Y, Liang S, Huo S, Wang X, Zuo Y, Cui D, Li W, Zhong Z, Zhong F
JournalViruses
PubMed ID31027293
Porcine parvovirus (PPV) is an important pathogen causing reproductive failure in pigs. PPV-induced cell apoptosis has been recently identified as being involved in PPV-induced placental tissue damages resulting in reproductive failure. However, the molecular mechanism was not fully elucidated. Here we demonstrate that PPV nonstructural protein 1 (NS1) can induce ... More
Reactive oxygen species (ROS) generation as an underlying mechanism of inorganic phosphate (P
AuthorsKhalid S, Yamazaki H, Socorro M, Monier D, Beniash E, Napierala D
JournalFree Radic Biol Med
PubMed ID32330587
Reactive Oxygen Species (ROS) are a natural byproduct of oxygen metabolism. At physiological levels, ROS regulate multiple cellular processes like proliferation, migration, and differentiation. Increased levels of ROS are associated with pathological conditions, such as inflammation and vascular calcification, where they elicit cytotoxic effects. These contrasting outcomes of ROS have ... More
High-protein diets increase cardiovascular risk by activating macrophage mTOR to suppress mitophagy.
AuthorsZhang X, Sergin I, Evans TD, Jeong SJ, Rodriguez-Velez A, Kapoor D, Chen S, Song E, Holloway KB, Crowley JR, Epelman S, Weihl CC, Diwan A, Fan D, Mittendorfer B, Stitziel NO, Schilling JD, Lodhi IJ, Razani B
JournalNat Metab
PubMed ID32128508
High protein diets are commonly utilized for weight loss, yet have been reported to raise cardiovascular risk. The mechanisms underlying this risk are unknown. Here, we show that dietary protein drives atherosclerosis and lesion complexity. Protein ingestion acutely elevates amino acid levels in blood and atherosclerotic plaques, stimulating macrophage mTOR ... More
Mitochondrial nucleoid morphology and respiratory function are altered in Drp1-deficient HeLa cells.
AuthorsOta A, Ishihara T, Ishihara N
JournalJ Biochem
PubMed ID31873747
Mitochondria are dynamic organelles that frequently divide and fuse with each other. The dynamin-related GTPase protein Drp1 has a key role in mitochondrial fission. To analyse the physiological roles of Drp1 in cultured human cells, we analysed Drp1-deficient HeLa cells established by genome editing using CRISPR/Cas9. Under fluorescent microscopy, not ... More
Resveratrol and HIV-protease inhibitors control UCP1 expression through opposite effects on p38 MAPK phosphorylation in human adipocytes.
AuthorsRavaud C, Paré M, Yao X, Azoulay S, Mazure NM, Dani C, Ladoux A
JournalJ Cell Physiol
PubMed ID31294462
Brown and brown-like adipocytes (BBAs) control thermogenesis and are detected in adult humans. They express UCP1, which transforms energy into heat. They appear as promising cells to fight obesity. Deciphering the molecular mechanisms leading to the browning of human white adipocytes or the whitening of BBAs represents a goal to ... More