Association of mitochondrial dysfunction and fatigue: A review of the literature

Kristin Filler, Debra Lyon, James Bennett, Nancy McCain, Ronald Elswick, Nada Lukkahatai, Leorey N. Saligan

Research output: Contribution to journalReview article

74 Scopus citations

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 1220 articles. After the 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.

Original languageEnglish (US)
Pages (from-to)12-23
Number of pages12
JournalBBA Clinical
Volume1
DOIs
StatePublished - Jun 2014

Keywords

  • Fatigue
  • Mitochondria
  • Review

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Medicine
  • Physiology (medical)

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  • Cite this

    Filler, K., Lyon, D., Bennett, J., McCain, N., Elswick, R., Lukkahatai, N., & Saligan, L. N. (2014). Association of mitochondrial dysfunction and fatigue: A review of the literature. BBA Clinical, 1, 12-23. https://doi.org/10.1016/j.bbacli.2014.04.001