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Updated: May 25, 2025

Analyses of Mitochondrial Calcium Influx in Isolated Mitochondria and Cultured Cells
Published on: April 27, 2018
Sirtuin-1 Regulates Mitochondrial Calcium Uptake Through Mitochondrial Calcium Uptake 1 (MICU1)
Xinyi Zhang1, Shuhu Liu1, Yanshan Su1
1Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Centre for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong Joint Laboratory for Psychiatric Disorders, Guangdong Provincial Key Laboratory of Psychiatric Disorders, Guangdong Basic Research Center of Excellence for Integrated Traditional and Western Medicine for Qingzhi Diseases, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Abstract:
Mitochondria play a central role in cell biological processes, functioning not only as producers of ATP but also as regulators of Ca2+ signaling. Mitochondrial calcium uptake occurs primarily through the mitochondrial calcium uniporter channel (mtCU), with the mitochondrial calcium uptake subunits 1, 2, and 3 (MICU1, MICU2, and MICU3) serving as the main regulatory components. Dysregulated mitochondrial calcium uptake is a hallmark of cellular degeneration. Sirtuin 1 (SIRT1), a key regulator of cellular metabolism, plays a critical role in aging and various neurodegenerative conditions. By blocking SIRT1 using EX527 or shSIRT1, we observed mitochondrial structural fragmentation as well as intensified and prolonged mitochondrial calcium overload. Our study revealed a direct interaction between SIRT1 and MICU1. Notably, SIRT1 inhibition resulted in reduced MICU1 expression, hence led to mitochondrial calcium overload, illustrating the unconventional role of SIRT1 in governing mitochondrial function.
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