Abstract
The mitochondrial calcium uniporter is an intensively investigated calcium channel, and its molecular components, structural features, and encoded genes have long been explored. Further studies have shown that the mitochondrial calcium unidirectional transporter (MCU) is a macromolecular complex related to intracellular and extracellular calcium regulation. Based on the current understanding, the MCU is crucial for maintaining cytosolic Ca2+ (cCa2+) homeostasis by modulating mitochondrial Ca2+ (mCa2+) uptake. The elevation of MCU-induced calcium levels is confirmed to be the main cause of mitochondrial reactive oxygen species (mROS) generation, which leads to disordered cellular metabolic patterns and cell death. In particular, in an I/R injury model, cancer cells, and adipocytes, MCU expression is maintained at high levels. As is well accepted, the AMPK/PGC-1α/SIRT3 pathway is believed to have an affinity for mROS formation and energy consumption. Therefore, we identified a link between MCU-related mROS formation and the AMPK/PGC-1α/SIRT3 signaling pathway in controlling cell metabolism and cell death, which may provide a new possibility of targeting the MCU to reverse relevant diseases.
Highlights
Previous studies have revealed that mitochondria regulate intracellular and extracellular calcium concentrations and signaling and are involved in a series of physiological and pathological processes, including energy metabolism, signaling regulation, smooth muscle contractility, cell proliferation, and cell death
It has been found that the uniporter is a complicated protein complex in humans that consists of four essential elements: mitochondrial calcium unidirectional transporter (MCU) [located at the mitochondrial inner transmembrane for ion MCU Regulates Cell Metabolism conduction that is inhibited by ruthenium red (RR) or Ru360] [3], MICU1 and MICU2 [4, 5], and EMRE [4]
Calcium uptake by mitochondria is attributed to three main functions: [1] maintenance of cellular metabolic homeostasis between the cytosol and mitochondria, [2] mediation of cCa2+ dynamics, and [3] modulation of various cell death pathways of apoptosis and necrosis [6,7,8]
Summary
Death Modulated by the AMPK/PGC-1α/SIRT3 Signaling Pathway. Further studies have shown that the mitochondrial calcium unidirectional transporter (MCU) is a macromolecular complex related to intracellular and extracellular calcium regulation. Based on the current understanding, the MCU is crucial for maintaining cytosolic Ca2+ (cCa2+) homeostasis by modulating mitochondrial Ca2+ (mCa2+) uptake. The elevation of MCU-induced calcium levels is confirmed to be the main cause of mitochondrial reactive oxygen species (mROS) generation, which leads to disordered cellular metabolic patterns and cell death. The AMPK/PGC-1α/SIRT3 pathway is believed to have an affinity for mROS formation and energy consumption. We identified a link between MCU-related mROS formation and the AMPK/PGC-1α/SIRT3 signaling pathway in controlling cell metabolism and cell death, which may provide a new possibility of targeting the MCU to reverse relevant diseases
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
