PhD Scientific Days 2026

Molecular Medicine 3.

The role of SERCA Ca²⁺ transporter in Autophagy

Name of the presenter

Kenzhebayeva, Zhanerke

Institute/workplace of the presenter

Etvos Lorand University

Authors

Zhanerke Kenzhebayeva^1,2, Sarolta Tóth², Ágnes Enyedi², Szabolcs Takáts¹
1: Department of Anatomy, Cell and Developmental Biology, Eotvos Lorand University, Budapest
2: Department of Transfusiology, Semmelweis University, Budapest

Text of the abstract

Introduction
The Sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) pumps Ca²⁺ into the ER, maintaining Ca²⁺ homeostasis and supporting downstream cellular processes, including autophagy. Autophagy is a lysosomal degradation pathway critical for cellular homeostasis under stress, proceeding through phagophore formation, autophagosome biogenesis, and autolysosomal cargo degradation. Although Ca²⁺ signaling and SERCA have been implicated in autophagy regulation, the precise molecular mechanisms remain poorly understood.
Aims
To investigate the role of SERCA and its interacting partners in the regulation of autophagy, with particular focus on early autophagic membrane dynamics in a Drosophila adipose tissue model.
Methods
SERCA and VMP1 (Vacuolar Membrane Protein 1) were silenced in Drosophila fat body using RNAi. Autophagic flux was assessed by monitoring the cargo receptor p62. Fluorescent immunolabeling and electron microscopy (EM) were used to characterize mitochondrial integrity, phagophore morphology, and VMP1 subcellular localization. Vps13D knockdown was additionally performed to probe functional interactions.
Results
Silencing of SERCA or VMP1 caused accumulation of p62, damaged mitochondria, and stalled phagophores unable to mature into autophagosomes. VMP1 subcellular localization was found to be SERCA-dependent. Knockdown of Vps13D, a known VMP1 interactor involved in mitophagy, phenocopied these defects, also resulting in downregulated autophagy and phagophore arrest.
Conclusion
SERCA plays a critical role in the early steps of autophagy, specifically in phagophore formation, likely through regulating VMP1 localization and its functional cooperation with Vps13D.
Funding:
Excellence Fund of ELTE (EKA_2022/045-P302-1)
NKFIH (OTKA FK_142508)
Hungarian Academy of Sciences (BO/00400/23)