Mechanical instability generated by Myosin 19 contributes to mitochondria cristae architecture and OXPHOS

Abstract

The folded mitochondria inner membrane-cristae is the structural foundation for oxidative phosphorylation (OXPHOS) and energy production. By mechanically simulating mitochondria morphogenesis, we speculate that efficient sculpting of the cristae is organelle non-autonomous. It has long been inferred that folding requires buckling in living systems. However, the tethering force for cristae formation and regulation has not been identified. Combining electron tomography, proteomics strategies, super resolution live cell imaging and mathematical modeling, we reveal that the mitochondria localized actin motor-myosin 19 (Myo19) is critical for maintaining cristae structure, by associating with the SAM-MICOS super complex. We discover that depletion of Myo19 or disruption of its motor activity leads to altered mitochondria membrane potential and decreased OXPHOS. We propose that Myo19 may act as a mechanical tether for effective ridging of the mitochondria cristae, thus sustaining the energy homeostasis essential for various cellular functions.

Regulation of oxidative phosphorylation by Nuclear myosin 1 protects cells from metabolic reprogramming and tumorigenesis in mice

“…Mitochondrial metabolism and more specifically, the relationship between OXPHOS and aerobic glycolysis plays, therefore, an important role in key cellular processes such as stemness and differentiation, but is also a defining feature during carcinogenesis. While several cytoskeletal proteins such β actin, Myosin II, or Myosin XIX have been shown to regulate mitochondrial dynamics directly (Korobova et al, 2014;Majstrowicz et al, 2021;Sato et al, 2022;Yang and Svitkina, 2019) and some of them are even present within the mitochondria (Shi et al, 2022;Xie et al, 2018), changes from OXPHOS to glycolysis are likely to require complex gene expression regulation yet to be fully understood.…”

Saturated fatty acids increase LPI to reduce FUNDC1 dimerization and stability and mitochondrial function

“…Cells were then incubated in CO 2 ‐free conditions for 1 h at 37°C, followed by the sequential addition of 1 μM Oligomycin, 4 μM FCCP and 1 μM Rotenone. The information on basal respiration and maximal respiration capacity of cells was calculated as described previously (Shi et al , 2022).…”

Extracting Mitochondrial Cristae Characteristics from 3D Focused Ion Beam Scanning Electron Microscopy Data

“…This approach is labor intensive, typically restricting analyses to a limited number of mitochondria. Most often subsequent evaluation of crista proporties has been performed in 2D [11, 12, 13, 10] and the validity of generalizations to 3D is questionable. Fortunately, studies of mitochondria and cristae in 3D based on manual reconstructions of individual mitochondria have also been performed for decades [14, 15, 16, 17, 18].…”