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Han Xu et al.
BMC nephrology, 19(1), 140-140 (2018-06-17)
The mechanism of podocyte apoptosis is not fully understood. In addition, the role of the inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) calcium regulation axis, which is located at sites of endoplasmic reticulum
Giampaolo Morciano et al.
Cell reports, 35(2), 108983-108983 (2021-04-15)
Preclinical models of ischemia/reperfusion injury (RI) demonstrate the deleterious effects of permeability transition pore complex (PTPC) opening in the first minutes upon revascularization of the occluded vessel. The ATP synthase c subunit (Csub) influences PTPC activity in cells, thus impacting
Bruno Seitaj et al.
Cells, 9(10) (2020-09-27)
The Transmembrane Bax Inhibitor-1 motif (TMBIM)-containing protein family is evolutionarily conserved and has been implicated in cell death susceptibility. The only member with a mitochondrial localization is TMBIM5 (also known as GHITM or MICS1), which affects cristae organization and associates
Fanxin Zeng et al.
Cancer research, 78(11), 2876-2885 (2018-03-14)
The receptor-interacting protein kinase 1 (RIPK1) is an essential signaling molecule in pathways for cell survival, apoptosis, and necroptosis. We report here that RIPK1 is upregulated in human colorectal cancer and promotes cell proliferation when overexpressed in a colon cancer
Horia Vais et al.
Cell reports, 14(3), 403-410 (2016-01-18)
The mitochondrial uniporter (MCU) is an ion channel that mediates Ca(2+) uptake into the matrix to regulate metabolism, cell death, and cytoplasmic Ca(2+) signaling. Matrix Ca(2+) concentration is similar to that in cytoplasm, despite an enormous driving force for entry
Sandra Zampieri et al.
Physiological reports, 4(24) (2017-01-01)
Age-related sarcopenia is characterized by a progressive loss of muscle mass with decline in specific force, having dramatic consequences on mobility and quality of life in seniors. The etiology of sarcopenia is multifactorial and underlying mechanisms are currently not fully
Chen-Wei Tsai et al.
Proceedings of the National Academy of Sciences of the United States of America, 114(17), 4388-4393 (2017-04-12)
The mitochondrial calcium uniporter is a Ca2+-activated Ca2+ channel complex mediating mitochondrial Ca2+ uptake, a process crucial for Ca2+ signaling, bioenergetics, and cell death. The uniporter is composed of the pore-forming MCU protein, the gatekeeping MICU1 and MICU2 subunits, and
Martina Kiefmann et al.
Cell death & disease, 8(8), e3005-e3005 (2017-08-25)
In adult respiratory distress syndrome (ARDS) pulmonary perfusion failure increases physiologic dead-space (V
Giulia Di Marco et al.
Cell reports, 30(7), 2321-2331 (2020-02-23)
Mitochondrial Ca2+ uptake depends on the mitochondrial calcium uniporter (MCU) complex, a highly selective channel of the inner mitochondrial membrane (IMM). Here, we screen a library of 44,000 non-proprietary compounds for their ability to modulate mitochondrial Ca2+ uptake. Two of
Jing Zhang et al.
The EMBO journal, 34(23), 2953-2970 (2015-10-27)
The EglN2/PHD1 prolyl hydroxylase is an important oxygen sensor contributing to breast tumorigenesis. Emerging studies suggest that there is functional cross talk between oxygen sensing and mitochondrial function, both of which play an essential role for sustained tumor growth. However
Luana Naia et al.
BMC biology, 19(1), 57-57 (2021-03-26)
Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with
An Xie et al.
Journal of the American Heart Association, 7(8) (2018-04-09)
Heart failure (HF) is associated with increased arrhythmia risk and triggered activity. Abnormal Ca2+ handling is thought to underlie triggered activity, and mitochondria participate in Ca2+ homeostasis. A model of nonischemic HF was induced in C57BL/6 mice by hypertension. Computer
Konstantin N Belosludtsev et al.
Biomolecules, 10(1) (2020-01-16)
The work examines the kinetic parameters of Ca2+ uptake via the mitochondrial calcium uniporter complex (MCUC) and the opening of the Ca2+-dependent permeability transition pore (MPT pore) in the liver and heart mitochondria of rats with high resistance (HR) and
Patrick J Doonan et al.
FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 28(11), 4936-4949 (2014-08-01)
Dysregulation of mitochondrial Ca(2+)-dependent bioenergetics has been implicated in various pathophysiological settings, including neurodegeneration and myocardial infarction. Although mitochondrial Ca(2+) transport has been characterized, and several molecules, including LETM1, have been identified, the functional role of LETM1-mediated Ca(2+) transport remains
Wei Chen et al.
Diabetes & vascular disease research, 14(6), 494-501 (2017-08-05)
Mitochondrial Ca Human umbilical vein endothelial cells were exposed to various glucose concentrations and to high glucose (30 mM) following mitochondrial calcium uniporter inhibition or activation with ruthenium red and spermine, respectively. Subsequently, mitochondrial calcium uniporter and mitochondrial calcium uniporter regulator
Xue Qiao et al.
Scientific reports, 7, 45379-45379 (2017-03-28)
Protein tyrosine phosphatase interacting protein 51 (PTPIP51) participates in multiple cellular processes, and dysfunction of PTPIP51 is implicated in diseases such as cancer and neurodegenerative disorders. However, there is no functional evidence showing the physiological or pathological roles of PTPIP51
Manish Verma et al.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(46), 11151-11165 (2017-10-19)
Mutations in leucine-rich repeat kinase 2 (LRRK2) contribute to development of late-onset familial Parkinson's disease (PD), with clinical features of motor and cognitive dysfunction indistinguishable from sporadic PD. Calcium dysregulation plays an important role in PD pathogenesis, but the mechanisms
Rajarshi Chakrabarti et al.
The Journal of cell biology, 217(1), 251-268 (2017-11-17)
Mitochondrial division requires division of both the inner and outer mitochondrial membranes (IMM and OMM, respectively). Interaction with endoplasmic reticulum (ER) promotes OMM division by recruitment of the dynamin Drp1, but effects on IMM division are not well characterized. We
Barbara A Miller et al.
Journal of cellular physiology (2019-01-15)
The mechanisms by which Trpm2 channels enhance mitochondrial bioenergetics and protect against oxidative stress-induced cardiac injury remain unclear. Here, the role of proline-rich tyrosine kinase 2 (Pyk2) in Trpm2 signaling is explored. Activation of Trpm2 in adult myocytes with H2
Lan Wei-LaPierre et al.
Archives of biochemistry and biophysics, 665, 122-131 (2019-03-16)
Mitochondrial flashes (mitoflashes) are stochastic events in the mitochondrial matrix detected by mitochondrial-targeted cpYFP (mt-cpYFP). Mitoflashes are quantal bursts of reactive oxygen species (ROS) production accompanied by modest matrix alkalinization and depolarization of the mitochondrial membrane potential. Mitoflashes are fundamental
Cesar Cardenas et al.
Science signaling, 13(640) (2020-07-16)
Spontaneous Ca2+ signaling from the InsP3R intracellular Ca2+ release channel to mitochondria is essential for optimal oxidative phosphorylation (OXPHOS) and ATP production. In cells with defective OXPHOS, reductive carboxylation replaces oxidative metabolism to maintain amounts of reducing equivalents and metabolic
Alice Rossi et al.
Cells, 10(2) (2021-01-27)
Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder in which learning, memory and cognitive functions decline progressively. Familial forms of AD (FAD) are caused by mutations in amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2)
Xianglan Quan et al.
The Journal of biological chemistry, 290(7), 4086-4096 (2014-12-31)
In pancreatic β-cells, ATP acts as a signaling molecule initiating plasma membrane electrical activity linked to Ca(2+) influx, which triggers insulin exocytosis. The mitochondrial Ca(2+) uniporter (MCU) mediates Ca(2+) uptake into the organelle, where energy metabolism is further stimulated for
Daniela M Arduino et al.
Molecular cell, 67(4), 711-723 (2017-08-19)
The mitochondrial calcium uniporter complex is essential for calcium (Ca2+) uptake into mitochondria of all mammalian tissues, where it regulates bioenergetics, cell death, and Ca2+ signal transduction. Despite its involvement in several human diseases, we currently lack pharmacological agents for
En Huang et al.
Nature communications, 8(1), 1399-1399 (2017-11-11)
Mutations in PTEN-induced kinase 1 (PINK1) result in a recessive familial form of Parkinson's disease (PD). PINK1 loss is associated with mitochondrial Ca
Dhanendra Tomar et al.
Cell reports, 26(13), 3709-3725 (2019-03-28)
Mitochondrial Ca2+ uniporter (MCU)-mediated Ca2+ uptake promotes the buildup of reducing equivalents that fuel oxidative phosphorylation for cellular metabolism. Although MCU modulates mitochondrial bioenergetics, its function in energy homeostasis in vivo remains elusive. Here we demonstrate that deletion of the Mcu
Alyssa A Lombardi et al.
Nature communications, 10(1), 4509-4509 (2019-10-06)
Fibroblast to myofibroblast differentiation is crucial for the initial healing response but excessive myofibroblast activation leads to pathological fibrosis. Therefore, it is imperative to understand the mechanisms underlying myofibroblast formation. Here we report that mitochondrial calcium (mCa2+) signaling is a
Sara C Sebag et al.
Experimental cell research, 362(2), 400-411 (2017-12-12)
Mitochondria are increasingly recognized as key mediators of acute cellular stress responses in asthma. However, the distinct roles of regulators of mitochondrial physiology on allergic asthma phenotypes are currently unknown. The mitochondrial Ca2+ uniporter (MCU) resides in the inner mitochondrial
Changhui Yu et al.
Oncotarget, 8(48), 83831-83844 (2017-11-16)
A shift from oxygen phosphorylation to aerobic glycolysis was known as the Warburg effect and a characteristic of cancer cell metabolism facilitating metastasis. Mitochondrial calcium uniporter (MCU), a key ion channel that mediates Ca We evaluated MCU overexpression or knock-down
Saverio Marchi et al.
The EMBO journal, 38(2) (2018-12-07)
Although mitochondria play a multifunctional role in cancer progression and Ca2+ signaling is remodeled in a wide variety of tumors, the underlying mechanisms that link mitochondrial Ca2+ homeostasis with malignant tumor formation and growth remain elusive. Here, we show that
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