Physical exercise and mitochondrial disease: Insights from a mouse model Articles uri icon

authors

  • FIUZA-LUCES, CARMEN
  • VALENZUELA, PEDRO L.
  • LAINE-MENENDEZ, SARA
  • FERNANDEZ DE LA TORRE, MIGUEL
  • BERMEJO GOMEZ, VERONICA
  • RUFIAN VAZQUEZ, LAURA
  • ARENAS, JOAQUIN
  • MARTIN, MIGUEL A.
  • LUCIA, ALEJANDRO
  • MORAN, MARIA

publication date

  • July 2019

start page

  • 1

end page

  • 10

volume

  • 10, 790

International Standard Serial Number (ISSN)

  • 1664-2295

abstract

  • Purpose: Mitochondrial diseases (MD) are among the most prevalent neuromuscular
    disorders. Unfortunately, no curative treatment is yet available. This study analyzed the
    effects of exercise training in an animal model of respiratory chain complex I deficiency,
    the Harlequin (Hq) mouse, which replicates the clinical features of this condition.
    Methods: Male heterozygous Harlequin (Hq/Y) mice were assigned to an 'exercise”
    (n = 10) or a 'sedentary” control group (n = 11), with the former being submitted
    to an 8 week combined exercise training intervention (aerobic + resistance training
    performed five times/week). Aerobic fitness, grip strength, and balance were assessed
    at the beginning and at the end of the intervention period in all the Hq mice.
    Muscle biochemical analyses (with results expressed as percentage of reference data
    from age/sex-matched sedentary wild-type mice [n = 12]) were performed at the
    end of the aforementioned period for the assessment of major molecular signaling
    pathways involved in muscle anabolism (mTOR activation) and mitochondrial biogenesis
    (proliferator activated receptor gamma co-activator 1α [PGC-1α] levels), and enzyme
    activity and levels of respiratory chain complexes, and antioxidant enzyme levels.
    Results: Exercise training resulted in significant improvements in aerobic fitness (−33
    ± 13 m and 83 ± 43 m for the difference post- vs. pre-intervention in total distance
    covered in the treadmill tests in control and exercise group, respectively, p = 0.014)
    and muscle strength (2 ± 4 g vs. 17 ± 6 g for the difference post vs. pre-intervention,
    p = 0.037) compared to the control group. Higher levels of ribosomal protein S6 kinase
    beta-1 phosphorylated at threonine 389 (156 ± 30% vs. 249 ± 30%, p = 0.028) and
    PGC-1α (82 ± 7% vs. 126 ± 19% p = 0.032) were observed in the exercise-trained
    mice compared with the control group. A higher activity of respiratory chain complexes
    I (75 ± 4% vs. 95 ± 6%, p = 0.019), III (79 ± 5% vs. 97 ± 4%, p = 0.031), and V (77
    ± 9% vs. 105 ± 9%, p = 0.024) was also found with exercise training. Exercised mice
    presented with lower catalase levels (204 ± 22% vs. 141 ± 23%, p = 0.036).
    Conclusion: In a mouse model of MD, a training intervention combining aerobic
    and resistance exercise increased aerobic fitness and muscle strength, and mild improvements were found for activated signaling pathways involved in muscle
    mitochondrial biogenesis and anabolism, OXPHOS complex activity, and redox status
    in muscle tissue.

subjects

  • Biology and Biomedicine
  • Medicine

keywords

  • rare diseases; mitochondrial diseases; oxphos; harlequin mutant mouse; resistance training; aif deficiency; respiratory chain complex i