Low abundance of Mfn2 protein correlates with reduced mitochondria‐SR juxtaposition and mitochondrial cristae density in human men skeletal muscle: Examining organelle measurements from TEM images
Mauricio Castro‐Sepúlveda, Rodrigo Fernández‐Verdejo, Mauro Tuñón‐Suárez, Jorge Morales‐Zúñiga, Mayarling F. Troncoso, Sebastián Jannas-Vela, Hermann Zbinden‐Foncea
Abstract
Abstract The role of mitofusin 2 (Mfn2) in the regulation of skeletal muscle (SM) mitochondria‐sarcoplasmic (SR) juxtaposition, mitochondrial morphology, mitochondrial cristae density (MCD), and SM quality has not been studied in humans. In in vitro studies, whether Mfn2 increases or decreases mitochondria‐SR juxtaposition remains controversial. Transmission electron microscopy (TEM) images are commonly used to measure the organelle juxtaposition, but the measurements are performed “by‐hand,” thus potentially leading to between‐rater differences. The purposes of this study were to: (1) examine the repeatability and reproducibility of mitochondrial‐SR juxtaposition measurement from TEM images of human SM between three raters with different experience and (2) compare the mitochondrial‐SR juxtaposition, mitochondrial morphology, MCD (stereological‐method), and SM quality (cross‐sectional area [CSA] and the maximum voluntary contraction [MVC]) between subjects with high abundance (Mfn2‐HA; n = 6) and low abundance (Mfn2‐LA; n = 6) of Mfn2 protein. The mitochondria‐SR juxtaposition had moderate repeatability and reproducibility, with the most experienced raters showing the best values. There were no differences between Mfn2‐HA and Mfn2‐LA groups in mitochondrial size, distance from mitochondria to SR, CSA, or MVC. Nevertheless, the Mfn2‐LA group showed lower mitochondria‐SR interaction, MCD, and VO 2max . In conclusion, mitochondrial‐SR juxtaposition measurement depends on the experience of the rater, and Mfn2 protein seems to play a role in the metabolic control of human men SM, by regulating the mitochondria‐SR interaction.