bims-cytox1 Biomed news on
Cytochrome oxidase subunit 1
Issue of 2017‒04‒21
seven papers selected by
Gavin McStay
New York Institute of Technology


  1. Oncotarget. 2017 Mar 31. doi: 10.18632/oncotarget.16766
    Abstract:  We have previously found that exogenously added lithocholic acid delays yeast chronological aging. We demonstrated that lithocholic acid enters the yeast cell, is sorted to mitochondria, resides in both mitochondrial membranes, changes the relative concentrations of different membrane phospholipids, triggers changes in the concentrations of many mitochondrial proteins, and alters some key aspects of mitochondrial functionality. We hypothesized that the lithocholic acid-driven changes in mitochondrial lipidome may have a causal role in the remodeling of mitochondrial proteome, which may in turn alter the functional state of mitochondria to create a mitochondrial pattern that delays yeast chronological aging. Here, we test this hypothesis by investigating how the ups1Δ, ups2Δ and psd1Δ mutations that eliminate enzymes involved in mitochondrial phospholipid metabolism influence the mitochondrial lipidome. We also assessed how these mutations affect the mitochondrial proteome, influence mitochondrial functionality and impinge on the efficiency of aging delay by lithocholic acid. Our findings provide evidence that 1) lithocholic acid initially creates a distinct pro-longevity pattern of mitochondrial lipidome by proportionally decreasing phosphatidylethanolamine and cardiolipin concentrations to maintain equimolar concentrations of these phospholipids, and by increasing phosphatidic acid concentration; 2) this pattern of mitochondrial lipidome allows to establish a specific, aging-delaying pattern of mitochondrial proteome; and 3) this pattern of mitochondrial proteome plays an essential role in creating a distinctive, geroprotective pattern of mitochondrial functionality.
    Keywords:  Gerotarget; aging; mitochondria; mitochondrial lipidome; mitochondrial proteome; yeast
  2. Biochim Biophys Acta. 2017 Apr 11. doi: 10.1016/j.bbamem.2017.04.007
    Abstract:  The regulation of glycerolipid biosynthesis is critical for homeostasis of cellular lipid stores and membranes. Here we review the role of lipin phosphatidic acid phosphatase enzymes in glycerolipid synthesis. Lipin proteins are unique among glycerolipid biosynthetic enzymes in their ability to transit among cellular membranes, rather than remain membrane tethered. We focus on the mechanisms that underlie lipin protein interactions with membranes and the versatile roles of lipins in several organelles, including the endoplasmic reticulum, mitochondria, endolysosomes, lipid droplets, and nucleus. We also review the corresponding physiological roles of lipins, which have been uncovered by the study of genetic lipin deficiencies. We propose that the growing body of knowledge concerning the biochemical and cellular activities of lipin proteins will be valuable for understanding the physiological functions of lipin proteins in health and disease. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo Escríba-Ruíz.
    Keywords:  Lipodystrophy; Phosphatidic acid phosphatase; Rhabdomyolysis; Triacylglycerol
  3. Am J Respir Crit Care Med. 2017 Apr 14. doi: 10.1164/rccm.201702-0311PP
    Abstract:  Chronic obstructive pulmonary disease (COPD) is a debilitating inflammatory lung disease associated with cigarette smoking and is third leading cause of death worldwide. With the recent emergence of genome wide association studies (GWAS), the identification of multiple COPD susceptibility genes has enhanced and expanded our understanding of the pathogenic mechanisms associated with this debilitating lung disease. An example of such a pathogenic mechanism is the role of iron metabolism in the onset and progression of COPD. Historic observations of iron dysregulation in COPD can now be enlightened by the recent revelations that genetic polymorphisms in the gene iron regulatory protein-2 (IRP-2) associate with COPD susceptibility. A functional role for IRP-2 is supported by IRP-2 overexpression in murine models, that demonstrates cellular and mitochondrial iron accumulation in the lung linked with manifestations of experimental COPD. Increased IRP2 may explain the excessive iron deposition in alveolar macrophages and tissue in smokers and in patients with COPD. Changes in IRP2 expression may also associate with systemic iron mismanagement, which may explain the prevalence of systemic iron deficiency and iron-deficiency anemia in patients with COPD. It may also help to explain why patients with COPD and/or iron deficiency manifest altered responses to hypoxia including erythropoiesis and pulmonary hypertension. We provide a concise review of the role of iron in the pathogenesis, susceptibility and progression of COPD and highlight the prospective therapeutic interventions for treating both local and systemic iron dysregulation.
    Keywords:  Anemia; COPD; Iron; Smoke
  4. Front Biosci (Landmark Ed). 2017 Jun 01. 22
    Abstract:  NOK is a potent oncogene that can transform normal cells to cancer cells. We hypothesized that NOK might impact cancer cell metabolism and histone acetylation. We show that NOK localizes in the mitochondria, and while it minimally impacts tricarboxylic acid (TCA) cycle, it markedly inhibits the process of electron transport and oxidative phosphorylation processes and dramatically enhances aerobic glycolysis in cancer cells. NOK promotes the mitochondrial-nuclear translocation of pyruvate dehydrogenase complex (PDC), and enhances histone acetylation in the nucleus. Together, these findings show that NOK mediates glycolysis and nuclear PDC associated histone acetylation.
  5. An Pediatr (Barc). 2017 Apr 11. doi: 10.1016/j.anpedi.2017.02.012
    Abstract:  INTRODUCTION: Pediatric acute liver failure (ALF) due to inherited metabolic diseases (IMD) is a rare life-threatening condition with a poor prognosis. Early intervention may be lifesaving. OBJECTIVE: To describe clinical presentation, investigation and outcomes of ALF related to IMD in young children. MATERIAL AND METHODS: Retrospective review of the medical records of children aged up to 24 months, admitted to a tertiary pediatric and neonatal Intensive Care Unit during a 27-year period, fulfilling the ALF criteria, with documented metabolic etiology. RESULTS: From 34 ALF cases, 18 were related to IMD: galactosemia (4), mitochondrial DNA depletion syndrome (MDS) (3), ornithine transcarbamilase deficiency (3), congenital defects of glycosylation (2), tyrosinemia type 1 (2), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (1), hereditary fructose intolerance (1), classic methylmalonic aciduria (1) and citrulinemia type 1 (1). The median age was 1.3 months. At least one previous suggestive sign/symptom of IMD (vomiting, failure to thrive, hypotonia or developmental delay) was observed in 67% of the cases. The most common physical signs at admission included: hepatomegaly (72%), jaundice (67%) and encephalopathy (44%). The peak laboratorial findings were: mean international normalizad ratio 4.5, median lactate 5mmol/L, mean bilirubin 201μmol/L, median alanine aminotransferase (ALT) 137 UI/L and median ammonia 177μmol/L. One patient was submitted to liver transplant in ALF context (MSD). The mortality rate was 44%. DISCUSSION: The identification of IMD as a frequent cause of ALF allowed specific therapeutic measures and adequate family counselling. Particular clinical features and moderated ALT and bilirubin levels can lead to its suspicion.
    Keywords:  Acute liver failure; Enfermedades metabólicas hereditarias; Fallo hepático agudo; Inherited metabolic diseases; Pediatric; Pediátrico
  6. Front Biosci (Schol Ed). 2017 Jun 01. 9
    Abstract:  Oxidative stress (OS) has been implicated in a wide array of diseases such as neurodegenerative disorders, autoimmune diseases, complex lifestyle diseases and cancer. OS is caused by an imbalance in production of Reactive Oxygen Species (ROS) and antioxidant defenses in the cell which results in the damage of cellular components, inactivate essential metabolic enzymes and disrupt signal transduction pathways. OS induces peroxidative damage to the sperm plasma membrane, DNA fragmentation in sperm nuclear/mitochondrial genome and causes dysregulation in levels of mRNAs/transcripts. OS induced sperm DNA damage is associated with male infertility, recurrent pregnancy loss (RPL), congenital malformations and high frequency of childhood disorders. OS induced pathologies are caused by endogenous and exogenous factors, majority of which, are modifiable. Antioxidant supplementation could help in relieving OS, however, its long-term usage may disrupt the intricate oxidation-reduction balance and  can lead to "Reductive Stress". Adoption of simple lifestyle interventions may relieve OS and can also aid in its management. This may improve overall quality of life (QOL) and can reduce prevalence of OS induced diseases.
  7. Biochim Biophys Acta. 2017 Apr 11. doi: 10.1016/j.bbamem.2017.04.006
    Abstract:  Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) are the most abundant phospholipids in all mammalian cell membranes. In the 1950s, Eugene Kennedy and co-workers performed groundbreaking research that established the general outline of many of the pathways of phospholipid biosynthesis. In recent years, the importance of phospholipid metabolism in regulating lipid, lipoprotein and whole-body energy metabolism has been demonstrated in numerous dietary studies and knockout animal models. The purpose of this review is to highlight the unappreciated impact of phospholipid metabolism on health and disease. Abnormally high, and abnormally low, cellular PC/PE molar ratios in various tissues can influence energy metabolism and have been linked to disease progression. For example, inhibition of hepatic PC synthesis impairs very low density lipoprotein secretion and changes in hepatic phospholipid composition have been linked to fatty liver disease and impaired liver regeneration after surgery. The relative abundance of PC and PE regulates the size and dynamics of lipid droplets. In mitochondria, changes in the PC/PE molar ratio affect energy production. We highlight data showing that changes in the PC and/or PE content of various tissues are implicated in metabolic disorders such as atherosclerosis, insulin resistance and obesity. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo Escríba-Ruíz.
    Keywords:  PC/PE ratio; energy metabolism; phosphatidylcholine; phosphatidylethanolamine