PhD Scientific Days 2026

Poster Session 3.U - Molecular Medicine

Investigation of the role of TRPM2 channel in mitochondrial Ca2+ uptake

Name of the presenter

Asztalos, Kristóf

Institute/workplace of the presenter

Department of Biochemistry

Authors

Kristóf Asztalos¹
1: Department of Biochemistry

Text of the abstract

Introduction:
TRPM2 is a Ca2+-gated cation ion channel located in the plasma membrane that is activated by the simultaneous intracellular binding of Ca2+ and ADPR ligands. The entering Ca2+ through the channel has a significant effect on mitochondrial function by enhancing mitochondrial Ca2+ uptake via mtCU. The increased [Ca2+]mit. may induce several processes leading to apoptosis, such as contributing to the opening of the mPTP or inducing ROS production.

Aims:
The aim of our experiments is to determine whether the entering Ca2+ through TRPM2 directly increases the [Ca2+]mit. via mtCU or whether this process occurs indirectly via the ER Ca2+ store. The direct effect would hypothesiz the close proximity of mtCU and TRPM2.

Methods:
To map this relationship, we use HEK293 cells that stably express TRPM2. To activate the channel, we induce intracellular ADPR production by H2O2. We follow the simultaneous changes in cytosolic and mitochondrial Ca2+ concentration with fluorescent microscopy. To register cytosolic Ca2+ concentration changes, we add fluorescent calcium dyes (Fura2-AM or Fura-FF AM), and to specifically detect [Ca2+]mit. changes, we express an organelle-specific calcium sensor (mtCepia). To increase the proximity between the organelles, we express a constitutive OMM–PM linker; this allows us to investigate the effect of spatial arrangement.

Results:
Our experiments have shown that induced ADPR production by H2O2 activates TRPM2 channels, which are tightly coupled to the rise of [Ca2+]cyt. and subsequently [Ca2+]mit.

Conclusion:
Our results show that the entering Ca2+ via TRPM2 has an important regulatory role in mitochondrial Ca2+ uptake; therefore, through the TRPM2 channel, mitochondrial functions involved in the apoptotic process may be regulated.

Funding:
Supported by the National Research, Development and Innovation Fund NKFIH KKP_22 grant 144199 and ADVANCED 149640. János Bolyai Research Scholarship of the Hungarian Academy of Sciences (BO/00238/25).

Name: dr. Asztalos Kristóf
University: Semmelweis University
Supervisor: dr. Bartók Ádám