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Visualization of lysosomal membrane proteins by cryo-electron tomography

ABSTRACT: Dysfunction in lysosomal membrane proteins and their associated complexes impairs the lysosome's essential role as a key signaling hub within the cell. This disruption underlies severe neurological disorders, such as lysosomal storage diseases and cancer. While direct visualization of the proteomic membrane environment of isolated lysosomes is crucial for advancing our understanding of its functions, it remains a significant challenge. To overcome this, we developed a method to enrich intact lysosomes using the essential lysosomal ion channel, transient receptor potential mucolipin 1. This enabled us to employ cryo electron tomography to reveal the heterogeneous molecular landscape of lysosomes. Notably, in concordance with quantitative mass spectrometry we identified protein densities on lysosomal membranes consistent with V-ATPase, Flotillin, clathrin-coated vesicles, mTORC1, HOPS, VPS13C, and dynein-dynactin. These findings demonstrate that our method offers a robust platform for advancing the structural and functional understanding of individual lysosomes, facilitating the visualization and resolution of endogenous protein complexes.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

DISEASE(S): Lysosomal Storage Disease

SUBMITTER: Marian Kalocsay

LAB HEAD: Vera Moiseenkova-Bell

PROVIDER: PXD055923 | Pride | 2025-10-17

REPOSITORIES: Pride

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			Action	DRS
	01252025_DHS_BM_IPLyso12plx_F1_C_001386_psc.mzXML	Mzxml
	01252025_DHS_BM_IPLyso12plx_F2_C_001387_psc.mzXML	Mzxml
	01252025_DHS_BM_IPLyso12plx_F3_C_001388_psc.mzXML	Mzxml
	01252025_DHS_BM_IPLyso12plx_F4_C_001389_psc.mzXML	Mzxml
	01252025_DHS_BM_IPLyso12plx_F5_C_001390_psc.mzXML	Mzxml

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