Mitochondrial Network Connectivity in Oxidative and Glycolytic Muscle

Identification: Glancy, Brian



Mitochondrial Network Connectivity in Oxidative and Glycolytic Muscle
Yuho Kim1, Christopher KE Bleck1, Brian Glancy1,2
1National Heart, Lung, and Blood Institute; 2National Institute of Arthritis and Musculoskeletal and Skin Diseases
Activation of skeletal muscle contraction occurs within milliseconds resulting in large, near-instantaneous increases in energy demand and necessitating rapid redistribution of energy throughout these large cells. We recently demonstrated that oxidative muscle fibers contain mitochondrial networks capable of electrical energy distribution. However, the mitochondrial network structure and energy distribution capability in the more powerful, yet more fatigable glycolytic muscle remain unclear. Here, we use volume electron microscopy to compare mitochondrial network structure and connectivity in oxidative and glycolytic muscle fibers. Focused ion beam scanning electron microscopy was performed on 2-4-month old C57BL/6N mouse muscles to assess cellular structures with 5-6 nm resolution in x, y, and z. In contrast to the large (48.4±0.6 µm3), grid-like networks of mitochondrial tubules found in oxidative fibers, mitochondria in glycolytic fibers formed smaller (4.7±0.1 µm3) subnetworks consisting primarily of thinner tubules oriented perpendicular to the contractile axis of the muscle fiber. There were also many fewer mitochondria per subnetwork in glycolytic muscle (7.6±0.2) compared to oxidative muscle (109.8±3.6). Individual mitochondria in glycolytic fibers (n=956) were smaller (0.29±0.00 µm3) than in oxidative fibers (0.63±0.01 µm3, n=503) but had a higher surface area to volume ratio(SA/V) (17.6±0.4 vs. 13.4±0.5 µm-1). Glycolytic mitochondria were also slightly less spherical (0.43±0.00 vs. 0.47±0.00) but no different in aspect ratio (3.22±0.06 vs. 3.22±0.07) compared to oxidative fibers. By comparing average network volume to that of a single mitochondrion, network connectivity provides a 74-fold increase in energy distribution capacity in oxidative muscle. Despite smaller, less connected mitochondrial networks compared to oxidative fibers, network connectivity in glycolytic fibers still provides a 10-fold advantage in energy distribution capacity over a single mitochondrion. Additionally, the larger SA/V of glycolytic mitochondria suggests a greater capacity for interacting with the cellular environment surrounding mitochondria which may be important for cell signaling and various import/export pathways.



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