title: Association of Mitochondrial Dysfunction and Fatigue: A Review of the Literature.
abstract: Fatigue is often described by patients as a lack of energy, mental or physical tiredness, diminished endurance, and prolonged recovery after physical activity. Etiologic mechanisms underlying fatigue are not well understood; however, fatigue is a hallmark symptom of mitochondrial disease, making mitochondrial dysfunction a putative biological mechanism for fatigue. Therefore, this review examined studies that investigated the association of markers of mitochondrial dysfunction with fatigue and proposes possible research directions to enhance understanding of the role of mitochondrial dysfunction in fatigue. A thorough search using PubMed, Scopus, Web of Science, and Embase databases returned 1,220 articles. After application of inclusion and exclusion criteria, a total of 25 articles meeting eligibility criteria were selected for full review. Dysfunctions in the mitochondrial structure, mitochondrial function (mitochondrial enzymes and oxidative/nitrosative stress), mitochondrial energy metabolism (ATP production and fatty acid metabolism), immune response, and genetics were investigated as potential contributors to fatigue. Carnitine was the most investigated mitochondrial function marker. Dysfunctional levels were reported in all the studies investigating carnitine; however, the specific type of carnitine that was dysfunctional varied. Genetic profiles were the second most studied mitochondrial parameter. Six common pathways were proposed: metabolism, energy production, protein transport, mitochondrial morphology, central nervous system dysfunction and post-viral infection. Coenzyme Q10 was the most commonly investigated mitochondrial enzyme. Low levels of Coenzyme Q10 were consistently associated with fatigue. Potential targets for further investigation were identified as well as gaps in the current literature.
authors.affiliation: Virginia Commonwealth University School of Nursing, 1100 East Leigh Street Richmond, Virginia 23298-0567, USA ; National Institutes of Health, National Institute of Nursing Research, 3 Center Drive, Building 3, Room 5E26, Bethesda, Maryland, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Filler
authors.affiliation: University of Florida College of Nursing, PO Box 100197 Gainesville, FL 32610-0197.
authors.forename: Debra
authors.initials: D
authors.lastname: Lyon
authors.affiliation: Virginia Commonwealth University School of Nursing, 1100 East Leigh Street Richmond, Virginia 23298-0567, USA.
authors.forename: James
authors.initials: J
authors.lastname: Bennett
authors.affiliation: Virginia Commonwealth University School of Nursing, 1100 East Leigh Street Richmond, Virginia 23298-0567, USA.
authors.forename: Nancy
authors.initials: N
authors.lastname: McCain
authors.affiliation: Virginia Commonwealth University School of Nursing, 1100 East Leigh Street Richmond, Virginia 23298-0567, USA.
authors.forename: Ronald
authors.initials: R
authors.lastname: Elswick
authors.affiliation: National Institutes of Health, National Institute of Nursing Research, 3 Center Drive, Building 3, Room 5E26, Bethesda, Maryland, USA.
authors.forename: Nada
authors.initials: N
authors.lastname: Lukkahatai
authors.affiliation: National Institutes of Health, National Institute of Nursing Research, 3 Center Drive, Building 3, Room 5E26, Bethesda, Maryland, USA.
authors.forename: Leorey N
authors.initials: LN
authors.lastname: Saligan
keywords: fatigue; mitochondria; review