VPS35 Deficiency Markedly Reduces the Proliferation of HEK293 Cells
Sujin Lee1, Soojin Park1, Hyewon Bang1
1College of Pharmacy, Catholic University of Daegu, Gyeongsan-si 38430, Gyeongbuk, Republic of Korea.
Genes
|February 27, 2026
Summary
VPS35 deficiency impairs cell growth and survival by disrupting retromer complex assembly, leading to increased apoptosis and mitochondrial fragmentation. Restoring VPS35 rescues these cellular defects, highlighting its critical role in cell cycle regulation and viability.
Area of Science:
- Cell Biology
- Molecular Biology
- Genetics
Background:
- The retromer complex is crucial for endosomal trafficking.
- Dysregulation of retromer components like VPS35 is implicated in neurodegenerative diseases.
- VPS35 knockout (KO) causes embryonic lethality, indicating its vital role.
Purpose of the Study:
- To investigate the cellular consequences of VPS35 deficiency.
- To understand the role of VPS35 in cell proliferation, apoptosis, and mitochondrial dynamics.
Main Methods:
- CRISPR/Cas9 was used to generate VPS35 KO HEK293 cells.
- Assessed retromer component expression, cell proliferation, apoptosis, and mitochondrial morphology.
- Utilized Western blotting, TUNEL assay, and confocal microscopy.
Main Results:
- VPS35 KO cells showed reduced proliferation and decreased VPS29/VPS26 expression, impairing retromer formation.
- Apoptosis markers (caspase-3, PARP, cytochrome C, p21) increased, while cell cycle markers (Ki-67, CDK4, cyclin D) decreased.
- VPS35 deletion induced mitochondrial fragmentation and altered expression of fission-related proteins.
Conclusions:
- VPS35 is essential for maintaining cell growth and survival.
- VPS35 modulates apoptosis, mitochondrial dynamics, and cell cycle progression.
- Restoration of VPS35 rescues cellular defects, confirming its critical functions.
Keywords:
HEK293 cellsVPS35cell proliferationendosomal traffickingmitochondrial dynamicsretromer complex
