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mitochondria

  • PARIS–DJ-1 Interaction Regulates Mitochondrial Functions in Cardiomyocytes, Which Is Critically Important in Cardiac Hypertrophy
    Research Article
    PARIS–DJ-1 Interaction Regulates Mitochondrial Functions in Cardiomyocytes, Which Is Critically Important in Cardiac Hypertrophy

    Mitochondrial dysfunction is one of the major pathological attributes of cardiac hypertrophy and is associated with reduced expression of PGC1α in cardiomyocytes. However, the transcriptional regulation of PGC1α remains elusive. Here, we show that parkin interacting substrate (PARIS), a KRAB zinc finger protein, prevented PGC1α transcription despite the induction of cardiomyocytes with hypertrophic stimuli. Moreover, PARIS expression...

    Dibyanti Mukherjee, Vivek Chander, Arun Bandyopadhyay
  • Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase
    Research Article
    Loss of Mitochondrial Localization of Human FANCG Causes Defective FANCJ Helicase

    Fanconi anemia (FA) is a unique DNA damage repair pathway. To date, 22 genes have been identified that are associated with the FA pathway. A defect in any of those genes causes genomic instability, and the patients bearing the mutation become susceptible to cancer. In our earlier work, we identified that Fanconi anemia protein G (FANCG) protects the mitochondria from oxidative stress. In this report, we have identified eight patients...

    Jagadeesh Chandra Bose K, Bishwajit Singh Kapoor, Kamal Mandal, Shubhrima Ghosh, Raveendra B. Mokhamatam, Sunil K. Manna, Sudit S. Mukhopadhyay
  • Determining the Bioenergetic Capacity for Fatty Acid Oxidation in the Mammalian Nervous System
    Research Article | Spotlight
    Determining the Bioenergetic Capacity for Fatty Acid Oxidation in the Mammalian Nervous System

    The metabolic state of the brain can greatly impact neurologic function. Evidence of this includes the therapeutic benefit of a ketogenic diet in neurologic diseases, including epilepsy. However, brain lipid bioenergetics remain largely uncharacterized. The existence, capacity, and relevance of mitochondrial fatty acid β-oxidation (FAO) in the brain are highly controversial, with few genetic tools available to evaluate the question. We...

    Cory J. White, Jieun Lee, Joseph Choi, Tiffany Chu, Susanna Scafidi, Michael J. Wolfgang
  • Anabolic SIRT4 Exerts Retrograde Control over TORC1 Signaling by Glutamine Sparing in the Mitochondria
    Research Article
    Anabolic SIRT4 Exerts Retrograde Control over TORC1 Signaling by Glutamine Sparing in the Mitochondria

    Anabolic and catabolic signaling mediated via mTOR and AMPK (AMP-activated kinase) have to be intrinsically coupled to mitochondrial functions for maintaining homeostasis and mitigate cellular/organismal stress. Although glutamine is known to activate mTOR, whether and how differential mitochondrial utilization of glutamine impinges on mTOR signaling has been less explored.

    Eisha Shaw, Manasi Talwadekar, Zeenat Rashida, Nitya Mohan, Aishwarya Acharya, Subhash Khatri, Sunil Laxman, Ullas Kolthur-Seetharam
  • Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells
    Research Article
    Peroxiredoxin 5 Inhibits Glutamate-Induced Neuronal Cell Death through the Regulation of Calcineurin-Dependent Mitochondrial Dynamics in HT22 Cells

    Glutamate is an essential neurotransmitter in the central nervous system (CNS). However, high glutamate concentrations can lead to neurodegenerative diseases. A hallmark of glutamate toxicity is high levels of reactive oxygen species (ROS), which can trigger Ca2+ influx and dynamin-related protein 1 (Drp1)-mediated mitochondrial fission. Peroxiredoxin 5 (Prx5) is a well-known cysteine-dependent peroxidase enzyme.

    ...
    Mi Hye Kim, Hong Jun Lee, Sang-Rae Lee, Hyun-Shik Lee, Jae-Won Huh, Yong Chul Bae, Dong-Seok Lee
  • The Role of Metabolic Flexibility in the Regulation of the DNA Damage Response by Nitric Oxide
    Research Article | Spotlight
    The Role of Metabolic Flexibility in the Regulation of the DNA Damage Response by Nitric Oxide

    In this report, we show that nitric oxide suppresses DNA damage response (DDR) signaling in the pancreatic β-cell line INS 832/13 and rat islets by inhibiting intermediary metabolism. Nitric oxide is known to inhibit complex IV of the electron transport chain and aconitase of the Krebs cycle.

    Bryndon J. Oleson, Katarzyna A. Broniowska, Chay Teng Yeo, Michael Flancher, Aaron Naatz, Neil Hogg, Vera L. Tarakanova, John A. Corbett
  • Myc Regulation of a Mitochondrial Trafficking Network Mediates Tumor Cell Invasion and Metastasis
    Research Article
    Myc Regulation of a Mitochondrial Trafficking Network Mediates Tumor Cell Invasion and Metastasis

    The Myc gene is a universal oncogene that promotes aggressive cancer, but its role in metastasis has remained elusive. Here, we show that Myc transcriptionally controls a gene network of subcellular mitochondrial trafficking that includes the atypical mitochondrial GTPases RHOT1 and RHOT2, the adapter protein TRAK2, the anterograde motor Kif5B, and an effector of mitochondrial fission, Drp1.

    Ekta Agarwal, Brian J. Altman, Jae Ho Seo, Irene Bertolini, Jagadish C. Ghosh, Amanpreet Kaur, Andrew V. Kossenkov, Lucia R. Languino, Dmitry I. Gabrilovich, David W. Speicher, Chi V. Dang, Dario C. Altieri
  • Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions
    Research Article
    Iron Supply via NCOA4-Mediated Ferritin Degradation Maintains Mitochondrial Functions

    Iron is an essential nutrient for mitochondrial metabolic processes, including mitochondrial respiration. Ferritin complexes store excess iron and protect cells from iron toxicity. Therefore, iron stored in the ferritin complex might be utilized under iron-depleted conditions.

    Motoki Fujimaki, Norihiko Furuya, Shinji Saiki, Taku Amo, Yoko Imamichi, Nobutaka Hattori
  • Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis
    Research Article
    Inner Mitochondrial Translocase Tim50 Is Central in Adrenal and Testicular Steroid Synthesis

    Adrenal and gonadal mitochondrial metabolic activity requires electrons from cofactors, cholesterol, and a substrate for rapid steroid synthesis, an essential requirement for mammalian survival. Substrate activity depends on its environment, which is regulated by chaperones and mitochondrial translocases.

    Himangshu S. Bose, Fadi Gebrail, Brendan Marshall, Elizabeth W. Perry, Randy M. Whittal
  • LONP1 Is Required for Maturation of a Subset of Mitochondrial Proteins, and Its Loss Elicits an Integrated Stress Response
    Research Article
    LONP1 Is Required for Maturation of a Subset of Mitochondrial Proteins, and Its Loss Elicits an Integrated Stress Response

    LONP1, an AAA+ mitochondrial protease, is implicated in protein quality control, but its precise role in this process remains poorly understood. In this study, we have investigated the role of human LONP1 in mitochondrial proteostasis and gene expression.

    Olga Zurita Rendón, Eric A. Shoubridge

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