An interactive deep learning-based approach reveals mitochondrial cristae topologies

• Published in: PLoS biology Vol. 21; no. 8; p. e3002246
• Main Authors: Suga, Shogo, Nakamura, Koki, Nakanishi, Yu, Humbel, Bruno M., Kawai, Hiroki, Hirabayashi, Yusuke
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 31.08.2023; Public Library of Science (PLoS)
• Subjects: Active learning; Algorithms; Archives & records; Atrophy; Biology and Life Sciences; Cell membranes; Cluster analysis; Clustering; Computer and Information Sciences; Cristae; Datasets; Deep learning; Dynamin; Editing; Electron microscopy; Image analysis; Image processing; Ion beams; Machine learning; Medicine and Health Sciences; Membranes; Metabolism; Metabolites; Mitochondria; Optic atrophy; Physical Sciences; Physiological aspects; Research and Analysis Methods; Scanning electron microscopy; Structure-function relationships; Tomography; Topology; Volumetric analysis; Workflow; Japan
• ISSN: 1545-7885; 1544-9173; 1545-7885
• DOI: 10.1371/journal.pbio.3002246

The convolution of membranes called cristae is a critical structural and functional feature of mitochondria. Crista structure is highly diverse between different cell types, reflecting their role in metabolic adaptation. However, their precise three-dimensional (3D) arrangement requires volumetric analysis of serial electron microscopy and has therefore been limiting for unbiased quantitative assessment. Here, we developed a novel, publicly available, deep learning (DL)-based image analysis platform called P ython-based h uman- i n-the- lo op w orkflow (PHILOW) implemented with a human-in-the-loop (HITL) algorithm. Analysis of dense, large, and isotropic volumes of focused ion beam-scanning electron microscopy (FIB-SEM) using PHILOW reveals the complex 3D nanostructure of both inner and outer mitochondrial membranes and provides deep, quantitative, structural features of cristae in a large number of individual mitochondria. This nanometer-scale analysis in micrometer-scale cellular contexts uncovers fundamental parameters of cristae, such as total surface area, orientation, tubular/lamellar cristae ratio, and crista junction density in individual mitochondria. Unbiased clustering analysis of our structural data unraveled a new function for the dynamin-related GTPase Optic Atrophy 1 (OPA1) in regulating the balance between lamellar versus tubular cristae subdomains.