Work

Inactivation of the High-Affinity Ca2+ Uptake System Delays the Amiodarone-Induced Ca2+ Influx in Yeast Ogataea parapolymorpha

Year: 2025

Type: article

Abstract: The antiarrhythmic drug amiodarone is toxic to yeast cells due to provoking Ca2+ entry into cytosol. Here we show that in Ogataea parapolymorpha, the loss of Cch1 or Mid1, which are the primary components of the high-affinity Ca2+ uptake system (HACS), leads to a delay in the rise of cytosolic Ca2+ concentration ([Ca2+]cyt) in response to amiodarone. This has negligible effect on the ability of the strain with the unaffected Ca2+ sequestration system to grow in the presence of amiodarone. Inactivation of the PMC1 gene encoding the Ca2+ ATPase involved in the cytosolic Ca2+ sequestration in the vacuole dramatically increases sensitivity to amiodarone, while inactivation of CCH1 or MID1 suppresses it. This correlates with a substantially lower [Ca2+]cyt rise in response to amiodarone when the genes encoding the HACS components are inactivated in the mutant lacking Pmc1. Similarly to sodium dodecyl sulfate, which has also been shown to increase [Ca2+]cyt, amiodarone causes activation of the Hog1 protein kinase involved in the cell cycle regulation. The role of HACS in the amiodarone-induced Ca2+ influx is discussed.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms262311386

Authors: Maria Kulakova, Maria Pakhomova, Victoria Bidiuk, Michael Agaphonov

Institutions: Russian Academy of Sciences, Federal Research Centre «Fundamentals of Biotechnology» of the Russian Academy of Sciences

Language: English

Topic: Fungal and yeast genetics research

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499