Pathogenic mitochondrial dysfunction and metabolic abnormalities

Walter H Moos; Douglas V Faller; Ioannis P Glavas; David N Harpp; Natalia Kamperi; Iphigenia Kanara; Krishna Kodukula; Anastasios N Mavrakis; Julie Pernokas; Mark Pernokas; Carl A Pinkert; Whitney R Powers; Kosta Steliou; Constantin Tamvakopoulos; Demetrios G Vavvas; Robert J Zamboni; Konstantina Sampani

doi:10.1016/j.bcp.2021.114809

Pathogenic mitochondrial dysfunction and metabolic abnormalities

Biochem Pharmacol. 2021 Nov:193:114809. doi: 10.1016/j.bcp.2021.114809. Epub 2021 Oct 19.

Authors

Walter H Moos¹, Douglas V Faller², Ioannis P Glavas³, David N Harpp⁴, Natalia Kamperi⁵, Iphigenia Kanara⁶, Krishna Kodukula⁷, Anastasios N Mavrakis⁸, Julie Pernokas⁹, Mark Pernokas⁹, Carl A Pinkert¹⁰, Whitney R Powers¹¹, Kosta Steliou¹², Constantin Tamvakopoulos⁵, Demetrios G Vavvas¹³, Robert J Zamboni⁴, Konstantina Sampani¹⁴

Affiliations

¹ Department of Pharmaceutical Chemistry, School of Pharmacy, University of California San Francisco, San Francisco, CA, USA. Electronic address: walter.moos@ucsf.edu.
² Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Cancer Research Center, Boston University School of Medicine, Boston, MA, USA.
³ Department of Ophthalmology, New York University School of Medicine, New York, NY, USA.
⁴ Department of Chemistry, McGill University, Montreal, QC, Canada.
⁵ Center for Clinical, Experimental Surgery and Translational Research Pharmacology-Pharmacotechnology, Biomedical Research Foundation, Academy of Athens, Athens, Greece.
⁶ Embassy of Greece in London, London, United Kingdom.
⁷ ShangPharma Innovation, South San Francisco, CA, USA.
⁸ Department of Medicine, Tufts University School of Medicine, St. Elizabeth's Medical Center, Boston, MA, USA.
⁹ Advanced Dental Associates of New England, Woburn, MA, USA.
¹⁰ Department of Pathobiology, College of Veterinary Medicine, Auburn University, Auburn, AL, USA.
¹¹ Department of Health Sciences, Boston University, Boston, MA, USA; Department of Anatomy, Boston University School of Medicine, Boston, MA, USA.
¹² Cancer Research Center, Boston University School of Medicine, Boston, MA, USA; PhenoMatriX, Inc., Natick, MA, USA.
¹³ Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; Retina Service, Angiogenesis Laboratory, Massachusetts Eye and Ear Infirmary, Boston, MA, USA.
¹⁴ Beetham Eye Institute, Joslin Diabetes Center, Boston, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA. Electronic address: konstantina.sampani@joslin.harvard.edu.

PMID: 34673016
DOI: 10.1016/j.bcp.2021.114809

Abstract

Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular microorganisms including bacteria and viruses are primary pathogenic drivers that cause disease. Missing from this statement are subcellular compartments, importantly mitochondria, which can be pathogenic by themselves, also serving as key metabolic disease intermediaries. The breakdown of food molecules provides chemical energy to power cellular processes, with mitochondria as powerhouses and ATP as the principal energy carrying molecule. Most animal cell ATP is produced by mitochondrial synthase; its central role in metabolism has been known for >80 years. Metabolic disorders involving many organ systems are prevalent in all age groups. Progressive pathogenic mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases, the most common phenotypic expression of inherited metabolic disorders. Confluent genetic, metabolic, and mitochondrial axes surface in diabetes, heart failure, neurodegenerative disease, and even in the ongoing coronavirus pandemic.

Keywords: Biochemical pathways; Diseases; Disorders; Dysfunction; Homeostasis; Metabolic abnormalities; Mitochondrial diseases; Pathogenesis; Pathogenesis and pathogenic drivers; Physiological networks; Reprogramming; Therapeutics.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
COVID-19 / metabolism*
COVID-19 / therapy
Diet, Healthy
Energy Metabolism / physiology
Humans
Metabolic Diseases / metabolism*
Metabolic Diseases / therapy
Mitochondria / metabolism*
Mitochondrial Diseases / metabolism*
Mitochondrial Diseases / therapy
Neurodegenerative Diseases / metabolism*
Neurodegenerative Diseases / therapy
Oxidative Stress / physiology