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Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?

Both bacteria and fungi produce extracellular proteinases since they need aminoacids for optimal reproduction. This may also occur inside host cells. Viral proteinases are produced during propagation inside host cells to supply amino acids for rapid synthesis of viral proteins, and/or to split poly-...

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Autores principales: Bongaerts, Ger P.A., van den Heuvel, Lambert P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131153/
https://www.ncbi.nlm.nih.gov/pubmed/17825998
http://dx.doi.org/10.1016/j.mehy.2007.06.035
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author Bongaerts, Ger P.A.
van den Heuvel, Lambert P.
author_facet Bongaerts, Ger P.A.
van den Heuvel, Lambert P.
author_sort Bongaerts, Ger P.A.
collection PubMed
description Both bacteria and fungi produce extracellular proteinases since they need aminoacids for optimal reproduction. This may also occur inside host cells. Viral proteinases are produced during propagation inside host cells to supply amino acids for rapid synthesis of viral proteins, and/or to split poly-protein molecules into single protein molecules, e.g., capside, and matrix and/or envelope proteins. In host cells the most profound, microbial proteinase-mediated effect is thought to be damage of the mitochondria, the site of oxidative energy generation. Two major effects can be imagined: (i) damage of proteinase-susceptible extra-mitochondrial membrane-associated proteins (razor blade effect), e.g., of mitochondrial transport proteins and of ATP:ADP translocase, and (ii) damage of intra-mitochondrial proteinase-susceptible proteins that are involved in the energy-generating processes. Although proteinases are not thought to invade and destroy mitochondria and essential intra-mitochondrial structures involved in energy generation, they can destroy non-mitochondrial encoded mitochondrial proteins during transport to the mitochondria, i.e., before incorporation inside the mitochondria in intra-mitochondrial structures. A secondary effect may be damage of liver cells that effect hepatic gluconeogenesis, the process that is involved in the synthesis of glucose from lactic acid. The proteinase may bring about inactivation of specific gluconeogenesis enzymes. This means that accumulated amounts of lactic acid cannot rapidly be reduced and consequently, such inactivation will increase intracellular and later even systemic acidification that may finally result in death. We postulate that both direct and indirect proteinase-mediated damage of mitochondria and gluconeogenesis enzymes, and consequently of human cellular energy generation, is an essential element in acute (e.g., influenza) and chronic (e.g., hepatitis B) intracellular infections.
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spelling pubmed-71311532020-04-08 Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases? Bongaerts, Ger P.A. van den Heuvel, Lambert P. Med Hypotheses Article Both bacteria and fungi produce extracellular proteinases since they need aminoacids for optimal reproduction. This may also occur inside host cells. Viral proteinases are produced during propagation inside host cells to supply amino acids for rapid synthesis of viral proteins, and/or to split poly-protein molecules into single protein molecules, e.g., capside, and matrix and/or envelope proteins. In host cells the most profound, microbial proteinase-mediated effect is thought to be damage of the mitochondria, the site of oxidative energy generation. Two major effects can be imagined: (i) damage of proteinase-susceptible extra-mitochondrial membrane-associated proteins (razor blade effect), e.g., of mitochondrial transport proteins and of ATP:ADP translocase, and (ii) damage of intra-mitochondrial proteinase-susceptible proteins that are involved in the energy-generating processes. Although proteinases are not thought to invade and destroy mitochondria and essential intra-mitochondrial structures involved in energy generation, they can destroy non-mitochondrial encoded mitochondrial proteins during transport to the mitochondria, i.e., before incorporation inside the mitochondria in intra-mitochondrial structures. A secondary effect may be damage of liver cells that effect hepatic gluconeogenesis, the process that is involved in the synthesis of glucose from lactic acid. The proteinase may bring about inactivation of specific gluconeogenesis enzymes. This means that accumulated amounts of lactic acid cannot rapidly be reduced and consequently, such inactivation will increase intracellular and later even systemic acidification that may finally result in death. We postulate that both direct and indirect proteinase-mediated damage of mitochondria and gluconeogenesis enzymes, and consequently of human cellular energy generation, is an essential element in acute (e.g., influenza) and chronic (e.g., hepatitis B) intracellular infections. Elsevier Ltd. 2008 2007-09-07 /pmc/articles/PMC7131153/ /pubmed/17825998 http://dx.doi.org/10.1016/j.mehy.2007.06.035 Text en Copyright © 2007 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Bongaerts, Ger P.A.
van den Heuvel, Lambert P.
Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?
title Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?
title_full Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?
title_fullStr Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?
title_full_unstemmed Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?
title_short Microbial proteinase inside human cells as anti-mitochondrial activity: A new virulence factor in infectious diseases?
title_sort microbial proteinase inside human cells as anti-mitochondrial activity: a new virulence factor in infectious diseases?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131153/
https://www.ncbi.nlm.nih.gov/pubmed/17825998
http://dx.doi.org/10.1016/j.mehy.2007.06.035
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