Transport of Calcium Ions into Mitochondria

Abstract

To uptake calcium ions of mitochondria is of significant functional connotation for cells, because calcium ions in mitochondria are involved in energy production, regulatory signals transfer, and mitochondrial permeability transition pore opening and even programmed cell death of apoptosis, further playing more roles in plant productivity and quality. Cytoplasmic calcium ions access into outer mitochondrial membrane (OMM) from voltage dependent anion-selective channel (VDAC) and were absorbed into inner mitochondrial membrane (IMM) by mitochondrial calcium uniporter (MCU), rapid mitochondrial calcium uptake (RaM) or mitochondrial ryanodine receptor (mRyR). Although both mitochondria and the mechanisms of calcium transport have been extensively studied, but there are still long-standing or even new challenges. Here we review the history and recent discoveries of the mitochondria calcium ions channel complex involved calcium assimilation, and discuss the role of calcium ions into mitochondria.

Regulation of Cell Death by Mitochondrial Transport Systems of Calcium and Bcl-2 Proteins

“…The RaM (RApid Mode of Ca 2+ uptake) mechanism is able to accumulate Ca 2+ up to a hundred times faster compared with the MCU multi-protein complex (no molecular structure responsible for this mechanism has yet been identified) [ 89 , 90 ]. It is transiently activated by low calcium concentrations (50–100 nM) and by high concentrations of Ruthenium Red [ 13 , 90 , 91 ]. This behavior contrasts sharply with MCU, which is activated by Ca 2+ concentrations higher than 500 nM.…”

“…RaM promotes mitochondria to rapidly sequester Ca 2+ at the beginning of each cytosolic Ca 2+ pulse, and rapidly recovers between pulses, allowing mitochondria to respond to repetitive Ca 2+ oscillations [ 13 , 91 ]. It is still speculated that RaM is just an additional state of the MCU multi-protein complex because of their similarity as well as the absence of RaM in MCU knockout mitochondria [ 65 , 90 , 91 ]. At present, the progress of research targeted on explaining the role of RaM in Ca 2+ influx at the molecular level is very limited.…”

A looming role of mitochondrial calcium in dictating the lung epithelial integrity and pathophysiology of lung diseases

“…The mitochondrial calcium uniporter (MCU) complex, Na + /Ca 2+ exchanger, and H + /Ca 2+ exchanger are the major proteins that help mitochondrial calcium migrate back and forth ( Finkel et al, 2015 ). To enter into the mitochondria, cytosolic Ca 2+ has to cross the outer mitochondrial membrane (OMM) and inner mitochondrial membrane (IMM) ( Xu et al, 2016 ). Cytosolic Ca 2+ entry across the membranes is regulated via certain special protein pores.…”

“…At a higher calcium level, EF hands of MICU1 and MICU2 get bounded by calcium. The inhibition of MICU2 is relaxed, MICU1 is activated which then helps MCU to facilitate the uptake of calcium ( Xu et al, 2016 ) . The main role of MICU1 and MICU2 dimers is to set a threshold of Ca 2+ for MCU thereby regulating the detrimental accumulation of Ca 2+ inside the matrix under basal conditions ( Giorgi et al, 2018 ).…”

Formal model of Parkinson’s disease neurons unveils possible causality links in the pathophysiology of the disease

“…Nature Reference L-Type NA E, MH, MB (Duda et al, 2016;Faber et al, 2007) T-Type NA E, MB (Branch et al, 2014;Poetschke et al, 2015) NCX 5000 Ca 2+ sec -1 1:3 (Ca 2+ : Na + ) MH, MB (Bers, 2002;Carafoli et al, 2001) PMCA NA 1 ATP per turn MB (Carafoli et al, 2001) Na/K ATPase 50 to 75% of the cell's ATP during one potential spike 2:3 (K + : Na + ) MB, MH (Gadsby, 2009;Howarth et al, 2012) mCU 1.10 6 Ca 2+ sec -1 Activated at high local concentration (~10 µM) MBH (Foskett and Madesh, 2014;Raffaello et al, 2016;Tan and Colombini, 2007) MAM 1.10 6 Ca 2+ sec -1 Activated at high local concentration (~10 µM) MB (Carafoli et al, 2001) mNCLX 5000 Ca 2+ sec -1 MB (Carafoli et al, 2001) RyR ~ 100 Ca 2+ sec -1 in average E, MB, MH (Carafoli et al, 2001;Raffaello et al, 2016) SERCA 200 Ca 2+ sec -1 E, MHB (Siegel George J. et al, 2006;Xu et al, 2016) KREBS 10 7 ATP sec -1 cell -1 10 7 ATP sec -1 cell -1 E (Mookerjee et al, 2017;Zimmerman et al, 2011) ETC SOD 10 5 -10 9 M -1 sec -1 (according to the physiological conditions and the literature) BM (Azadmanesh and Borgstahl, 2018;Sheng et al, 2014) Fenton Reaction 50 mol -1 dm 3 s -1 V (Kremer, 2003) DMT1 NA YBM (Andrews and Schmidt, 2007;Hadzhieva et al, 2014) TfR NA FTN1 NA…”