J Clin Neurol.  2017 Oct;13(4):359-365. 10.3988/jcn.2017.13.4.359.

Ultrastructural Changes in Skeletal Muscle of Infants with Mitochondrial Respiratory Chain Complex I Defects

• Mun JY
• Jung MK
• Kim SH
• Eom S
• Han SS
• Lee YM

• KMID: 2392131
• DOI: http://doi.org/10.3988/jcn.2017.13.4.359

Abstract

BACKGROUND AND PURPOSE
The pathogenesis of mitochondrial disease (MD) involves the disruption of cellular energy metabolism, which results from defects in the mitochondrial respiratory chain complex (MRC). We investigated whether infants with MRC I defects showed ultrastructural changes in skeletal muscle.
METHODS
Twelve infants were enrolled in this study. They were initially evaluated for unexplained neurodegenerative symptoms, myopathies, or other progressive multiorgan involvement, and underwent muscle biopsies when MD was suspected. Muscle tissue samples were subjected to biochemical enzyme assays and observation by transmission electron microscopy. We compared and analyzed the ultrastructure of skeletal muscle tissues obtained from patients with and without MRC I defects.
RESULTS
Biochemical enzyme assays confirmed the presence of MRC I defects in 7 of the 12 patients. Larger mitochondria, lipid droplets, and fused structures between the outer mitochondrial membrane and lipid droplets were observed in the skeletal muscles of patients with MRC I defects.
CONCLUSIONS
Mitochondrial functional defects in MRC I disrupt certain activities related to adenosine triphosphate synthesis that produce changes in the skeletal muscle. The ultrastructural changes observed in the infants in this study might serve as unique markers for the detection of MD.

Keyword

mitochondria; respiratory chain complex; infant; muscle pathology; ultrastructure; transmission electron microscopy

MeSH Terms

Adenosine Triphosphate
Biopsy
Electron Transport*
Energy Metabolism
Enzyme Assays
Humans
Infant*
Lipid Droplets
Microscopy, Electron, Transmission
Mitochondria
Mitochondrial Diseases
Mitochondrial Membranes
Muscle, Skeletal*
Muscular Diseases
Adenosine Triphosphate

Figure

• 

  Fig. 1 Transmission electron microscopy of human mitochondria in skeletal muscle. Mitochondria in muscle without (A) and with (B and C) MRC I defects. Mitochondrial size is shown in (D). Changes in the percentage area of cristae and the mitochondrial size are shown in (E). The number of mitochondria is counted in (F). The number of mitochondria per square micron was multiplied by 100 to calculate the number of filaments per 100 µm2. Scale bars indicate 100 nm. MRC: mitochondrial respiratory chain complex.

• 

  Fig. 2 Effects of mitochondrial dysfunction on intramyocellular lipid droplets. These are images from patients without (A and C) and with (B and D) MRC I defects. Arrows indicate lipid droplets. Electron tomograms are illustrated in (E). The 3D reconstruction of mitochondria and lipid droplets are shown in (F). The outer membrane of the mitochondria is shown in pink and cristae in green. Sizes of lipid droplets were presented as the mean values for 50 lipid droplets measured in each group (G). Scale bars indicate 5 µm (A and B), 2 µm (C and D), and 100 nm (E). Li: lipid droplet, M: mitochondria, MRC: mitochondrial respiratory chain complex.

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