Neurological disorders are closely related to disruptions in lipid homeostasis, particularly within mitochondria and lysosomes, leading to defects in membrane dynamics and organelle function.
Our lab focuses on dissecting the in situ structure and functional mechanisms of macromolecule-driven membrane shaping and remodeling across cellular, tissue, and organismal scales.
Bridge-like lipid transfer proteins (BLTPs) are a specialized group of proteins with a hydrophobic channel that runs along their entire length. This unique structure allows them to transport lipids in vitro and likely in vivo. They are proposed to function in membrane remodeling, and are essential for cellular function and brain health. However, their structure, function and regulation within cells remain poorly understood.
Our main approach is cellular cryo-ET, integrated with correlated light-electron microscopy, cryo-lift-out, cryo-FIB milling, and FIB-SEM. These techniques allow us to directly visualize macromolecules and their associated subcellular compartments at molecular resolution within lifelike cells, tissues or intact organisms.
We previously visualized a member of BLTP family protein, VPS13C, in its natural context within cells, contacts between the endoplasmic reticulum (ER) and lysosomes. Its in situ architecture at these contacts is consistent with its functioning as a bridge that allows lipids to slide between closely apposed bilayers along a hydrophobic groove that runs along its entire length (Cai et al., PNAS, 2022, PMID: 35858323)
We investigated the mechanisms underlying mitophagy membrane expansion during development and unexpectedly found that the ER directly supplies membrane to support extensive mitophagophore growth (Huang, Zheng et al., Autophagy, 2026, PMID: 41949493).
We revealed RIBEYE assemblies, which organize synaptic vesicles at ribbon synapses, undergo dramatic structural transitions (Liu, Wang, Zheng, Niu et al., Vita, 2026).
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