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𝗖𝗿𝘆𝗼𝗴𝗲𝗻𝗶𝗰 𝗘𝗹𝗲𝗰𝘁𝗿𝗼𝗻 𝗧𝗼𝗺𝗼𝗴𝗿𝗮𝗽𝗵𝘆 (𝗖𝗿𝘆𝗼-𝗘𝗧) captures intermediate structures of dynamic cellular endomembrane systems. 𝘝𝘪𝘵𝘳𝘪𝘧𝘪𝘤𝘢𝘵𝘪𝘰𝘯 of samples and 𝘤𝘳𝘺𝘰-𝘌𝘛 have unlocked our capabilities to observe cellular ultrastructures at near-native states, which has previously eluded researchers due to the disadvantages of the sample preparation (fixation and dehydration) of conventional electron microscopy. As such, 𝘴𝘵𝘳𝘶𝘤𝘵𝘶𝘳𝘢𝘭 𝘪𝘯𝘵𝘦𝘳𝘮𝘦𝘥𝘪𝘢𝘵𝘦𝘴 𝘥𝘶𝘳𝘪𝘯𝘨 𝘵𝘩𝘦 𝘧𝘰𝘳𝘮𝘢𝘵𝘪𝘰𝘯 𝘰𝘧 𝘪𝘯𝘵𝘳𝘢𝘭𝘶𝘮𝘪𝘯𝘢𝘭 𝘷𝘦𝘴𝘪𝘤𝘭𝘦𝘴 are still poorly understood, despite the importance of trafficking and remodeling of endomembranes in cell function. This study, published in Nature Communications, presents visual evidence of 𝗹𝗼𝗻𝗴-𝗹𝗶𝘃𝗲𝗱 𝗵𝗲𝗺𝗶𝗳𝘂𝘀𝗼𝗺𝗲𝘀 and suggests this vesicular structure as 𝗮𝗻 𝗮𝗹𝘁𝗲𝗿𝗻𝗮𝘁𝗶𝘃𝗲 𝗽𝗮𝘁𝗵𝘄𝗮𝘆 𝗳𝗼𝗿 𝗺𝘂𝗹𝘁𝗶𝘃𝗲𝘀𝗶𝗰𝘂𝗹𝗮𝗿 𝗯𝗼𝗱𝘆 (𝗠𝗩𝗕𝘀) formation. Key points that were derived solely with extensive cryo-ET imaging and visual examination were:    • 𝗛𝗲𝗺𝗶𝗳𝘂𝘀𝗼𝗺𝗲𝘀 are 𝙝𝙚𝙩𝙚𝙧𝙤𝙩𝙮𝙥𝙞𝙘 𝙛𝙪𝙨𝙚𝙙 𝙫𝙚𝙨𝙞𝙘𝙡𝙚𝙨 with an extended hemifused diaphgram and a 𝙥𝙧𝙤𝙩𝙚𝙤𝙡𝙞𝙥𝙞𝙙 𝙣𝙖𝙣𝙤𝙙𝙧𝙤𝙥𝙡𝙚𝙩   • Two types of hemifusomes: a "𝘥𝘪𝘳𝘦𝘤𝘵" 𝘤𝘰𝘯𝘧𝘰𝘳𝘮𝘢𝘵𝘪𝘰𝘯 in which the smaller vesicle is on the cytoplasmic side of the larger vesicle, and a "𝘧𝘭𝘪𝘱𝘱𝘦𝘥" 𝘤𝘰𝘯𝘧𝘰𝘳𝘮𝘢𝘵𝘪𝘰𝘯 in which the smaller vesicle is fused to the luminal side of the larger one.   • The 𝘷𝘦𝘴𝘪𝘤𝘭𝘦 𝘤𝘰𝘯𝘵𝘦𝘯𝘵 of the heterotypic vesicles differ, with lumen of the smaller vesicle appearing smooth and translucent, while the lumen of the larger one presents a fine-grained texture, similar to ribosome associated vesicles and endosome-like vesicles.   • The 𝗽𝗿𝗼𝘁𝗲𝗼𝗹𝗶𝗽𝗶𝗱 𝗻𝗮𝗻𝗼𝗱𝗿𝗼𝗽𝗹𝗲𝘁 is suggested as the 𝘪𝘯𝘪𝘵𝘪𝘢𝘵𝘰𝘳 𝘢𝘯𝘥 𝘮𝘦𝘥𝘪𝘢𝘵𝘰𝘳 𝘰𝘧 𝘩𝘦𝘮𝘪𝘧𝘶𝘴𝘰𝘮𝘦 𝘧𝘰𝘳𝘮𝘢𝘵𝘪𝘰𝘯.   • Gold nanoparticle tracking experiments distinguished hemifusomes as a different population of vesicles than endosomes.   • "Flipped" compound hemifusomes are proposed as an 𝘢𝘭𝘵𝘦𝘳𝘯𝘢𝘵𝘪𝘷𝘦 𝘱𝘢𝘵𝘩𝘸𝘢𝘺 𝘵𝘰 𝘵𝘩𝘦 𝘧𝘰𝘳𝘮𝘢𝘵𝘪𝘰𝘯 𝘰𝘧 𝘔𝘝𝘉𝘴. This myriad of initial information about hemifusomes were all derived from cryo-ET observation, showcasing the power of microscopy as an starting point for understanding the unknown. 📖 Read the paper here: https://lnkd.in/gKE-Ab7T 😍 Interested elevating your research with advanced electron microscopy? Visit our website for more details: https://lnkd.in/eB4Q6rfh #ElectronMicroscopy #CryoElectronTomography #CryoET