Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study

被引:191
作者
Picard, Martin [1 ,2 ,3 ,4 ]
White, Kathryn [5 ]
Turnbull, Douglass M. [1 ,6 ,7 ]
机构
[1] Newcastle Univ, Mitochondrial Res Grp, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[2] McGill Univ, Dept Kinesiol & Phys Educ, Montreal, PQ, Canada
[3] Univ Penn, Childrens Hosp Philadelphia, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA
[4] Univ Penn, Philadelphia, PA 19104 USA
[5] Newcastle Univ, EM Res Serv, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[6] Newcastle Univ, Inst Ageing & Hlth, Newcastle Univ Ctr Brain Ageing & Vital, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[7] Newcastle Univ, Inst Ageing & Hlth, Wellcome Trust Ctr Mitochondrial Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
基金
英国惠康基金; 加拿大自然科学与工程研究理事会; 英国工程与自然科学研究理事会; 英国生物技术与生命科学研究理事会; 英国经济与社会研究理事会; 英国医学研究理事会;
关键词
skeletal muscle mitochondria; myofiber; outer mitochondrial membrane; scanning and transmission electron microscopy; mitochondrial reticulum; INTERMYOFIBRILLAR MITOCHONDRIA; EMBRYONIC-DEVELOPMENT; OPA1; MUTATIONS; FUSION; FISSION; RETICULUM; FIBERS; DEGRADATION; METABOLISM; MITOFUSINS;
D O I
10.1152/japplphysiol.01096.2012
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Mitochondrial morphology, topology, and membrane interactions in skeletal muscle: a quantitative three-dimensional electron microscopy study. J Appl Physiol 114: 161-171, 2013. First published October 25, 2012; doi:10.1152/japplphysiol.01096.2012.-Dynamic remodeling of mitochondrial morphology through membrane dynamics are linked to changes in mitochondrial and cellular function. Although mitochondrial membrane fusion/fission events are frequent in cell culture models, whether mitochondrial membranes dynamically interact in postmitotic muscle fibers in vivo remains unclear. Furthermore, a quantitative assessment of mitochondrial morphology in intact muscle is lacking. Here, using electron microscopy (EM), we provide evidence of interacting membranes from adjacent mitochondria in intact mouse skeletal muscle. Electron-dense mitochondrial contact sites consistent with events of outer mitochondrial membrane tethering are also described. These data suggest that mitochondrial membranes interact in vivo among mitochondria, possibly to induce morphology transitions, for kiss-and-run behavior, or other processes involving contact between mitochondrial membranes. Furthermore, a combination of freeze-fracture scanning EM and transmission EM in orthogonal planes was used to characterize and quantify mitochondrial morphology. Two subpopulations of mitochondria were studied: subsarcolemmal (SS) and intermyofibrillar (IMF), which exhibited significant differences in morphological descriptors, including form factor (means +/- SD for SS: 1.41 +/- 0.45 vs. IMF: 2.89 +/- 1.76, P < 0.01) and aspect ratio (1.97 +/- 0.83 vs. 3.63 +/- 2.13, P < 0.01) and circularity (0.75 +/- 0.16 vs. 0.45 +/- 0.22, P < 0.01) but not size (0.28 +/- 0.31 vs. 0.27 +/- 0.20 mu m(2)). Frequency distributions for mitochondrial size and morphological parameters were highly skewed, suggesting the presence of mechanisms to influence mitochondrial size and shape. In addition, physical continuities between SS and IMF mitochondria indicated mixing of both subpopulations. These data provide evidence that mitochondrial membranes interact in vivo in mouse skeletal muscle and that factors may be involved in regulating skeletal muscle mitochondrial morphology.
引用
收藏
页码:161 / 171
页数:11
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