Mitochondrial Reticulum in Skeletal Muscles: Proven and Hypothetical Functions

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Lora E. Bakeeva¹, Valeriya B. Vays¹, Irina M. Vangeli¹, Chupalav M. Eldarov^1,2, Vasily A. Popkov¹, Ljubava D. Zorova^1,2, Savva D. Zorov^1,3, and Dmitry B. Zorov^1,2,a*

¹Belozersky Research Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia

²Kulakov National Medical Research Center of Obstetrics, Gynecology, and Perinatology; Ministry of Health of the Russian Federation, 117997 Moscow, Russia

³Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russia

^* To whom correspondence should be addressed.

Received: July 8, 2025; Revised: October 12, 2025; Accepted: October 19, 2025

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The mitochondrial reticulum of skeletal muscles has been characterized in the 1970-80s. It has been suggested and then proven its role is delivering energy in a form of transmembrane potential on the mitochondrial inner membrane throughout the cell volume, followed by ATP synthesis by the mitochondrial ATP synthase. However, the data on the mitochondrial ultrastructure still remains a subject to criticism. To exclude the possibility of artifacts caused by the sample preparation for electron microscopy, we compared the structure of mitochondria in the ultrathin sections of muscle fibers observed by electron microscopy and in intact fibers stained with a membrane potential-dependent dye and visualized by confocal microscopy. The comparison was carried out for mice and naked mole rats known for their superior longevity. The obtained results confirmed previous findings regarding the structure of mitochondrial reticulum. A model suggesting the functioning of giant mitochondria as intracellular structures preventing tissue hypoxia was proposed.

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KEY WORDS: mitochondria, ultrastructure, reticulum, membrane potential, hypoxia, oxygen transport, mouse, naked mole rat

DOI: 10.1134/S000629792560190X

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