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Activity of the mitochondrial calcium uniporter varies greatly between tissues.

Fieni F, Lee SB, Jan YN, Kirichok Y - Nat Commun (2012)

Bottom Line: Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues.As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake.Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.

ABSTRACT
The mitochondrial calcium uniporter is a highly selective channel responsible for mitochondrial Ca(2+) uptake. The mitochondrial calcium uniporter shapes cytosolic Ca(2+) signals, controls mitochondrial ATP production, and is involved in cell death. Here using direct patch-clamp recording from the inner mitochondrial membrane, we compare mitochondrial calcium uniporter activity in mouse heart, skeletal muscle, liver, kidney and brown fat. Surprisingly, heart mitochondria show a dramatically lower mitochondrial calcium uniporter current density than the other tissues studied. Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues. As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake. Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

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Related in: MedlinePlus

IMCU is time-independent and blocked by RuR in skeletal muscle and heart(a) IMCU elicited by a voltage-step protocol (as indicated on top, ΔV= 20 mV) in skeletal muscle (left panel) and heart (right panel). (b) IMCU recorded in the presence of 100 μM Ca2+ (blue trace) was completely inhibited by 50 nM RuR (red trace) both in skeletal muscle (left panel) and heart (right panel). The black traces indicate the baseline recorded in the absence of Ca2+ in the bath. Currents were normalized to the membrane capacitance to compare IMCU in heart and skeletal muscle. Voltage-ramp protocol is indicated on top.
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Figure 2: IMCU is time-independent and blocked by RuR in skeletal muscle and heart(a) IMCU elicited by a voltage-step protocol (as indicated on top, ΔV= 20 mV) in skeletal muscle (left panel) and heart (right panel). (b) IMCU recorded in the presence of 100 μM Ca2+ (blue trace) was completely inhibited by 50 nM RuR (red trace) both in skeletal muscle (left panel) and heart (right panel). The black traces indicate the baseline recorded in the absence of Ca2+ in the bath. Currents were normalized to the membrane capacitance to compare IMCU in heart and skeletal muscle. Voltage-ramp protocol is indicated on top.

Mentions: In both heart and skeletal muscle, IMCU elicited by voltage steps was primarily time-independent (Fig. 2a) and apparently lacked Ca2+-dependent inactivation, similar to what was previously reported for IMCU in COS7 cell mitochondria. As expected, in both tissues, IMCU was completely blocked by 50 nM RuR, a potent blocker of the MCU17,18 (Fig. 2b).


Activity of the mitochondrial calcium uniporter varies greatly between tissues.

Fieni F, Lee SB, Jan YN, Kirichok Y - Nat Commun (2012)

IMCU is time-independent and blocked by RuR in skeletal muscle and heart(a) IMCU elicited by a voltage-step protocol (as indicated on top, ΔV= 20 mV) in skeletal muscle (left panel) and heart (right panel). (b) IMCU recorded in the presence of 100 μM Ca2+ (blue trace) was completely inhibited by 50 nM RuR (red trace) both in skeletal muscle (left panel) and heart (right panel). The black traces indicate the baseline recorded in the absence of Ca2+ in the bath. Currents were normalized to the membrane capacitance to compare IMCU in heart and skeletal muscle. Voltage-ramp protocol is indicated on top.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3818247&req=5

Figure 2: IMCU is time-independent and blocked by RuR in skeletal muscle and heart(a) IMCU elicited by a voltage-step protocol (as indicated on top, ΔV= 20 mV) in skeletal muscle (left panel) and heart (right panel). (b) IMCU recorded in the presence of 100 μM Ca2+ (blue trace) was completely inhibited by 50 nM RuR (red trace) both in skeletal muscle (left panel) and heart (right panel). The black traces indicate the baseline recorded in the absence of Ca2+ in the bath. Currents were normalized to the membrane capacitance to compare IMCU in heart and skeletal muscle. Voltage-ramp protocol is indicated on top.
Mentions: In both heart and skeletal muscle, IMCU elicited by voltage steps was primarily time-independent (Fig. 2a) and apparently lacked Ca2+-dependent inactivation, similar to what was previously reported for IMCU in COS7 cell mitochondria. As expected, in both tissues, IMCU was completely blocked by 50 nM RuR, a potent blocker of the MCU17,18 (Fig. 2b).

Bottom Line: Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues.As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake.Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, University of California, San Francisco, San Francisco, California 94158, USA.

ABSTRACT
The mitochondrial calcium uniporter is a highly selective channel responsible for mitochondrial Ca(2+) uptake. The mitochondrial calcium uniporter shapes cytosolic Ca(2+) signals, controls mitochondrial ATP production, and is involved in cell death. Here using direct patch-clamp recording from the inner mitochondrial membrane, we compare mitochondrial calcium uniporter activity in mouse heart, skeletal muscle, liver, kidney and brown fat. Surprisingly, heart mitochondria show a dramatically lower mitochondrial calcium uniporter current density than the other tissues studied. Similarly, in Drosophila flight muscle, mitochondrial calcium uniporter activity is barely detectable compared with that in other fly tissues. As mitochondria occupy up to 40% of the cell volume in highly metabolically active heart and flight muscle, low mitochondrial calcium uniporter activity is likely essential to avoid cytosolic Ca(2+) sink due to excessive mitochondrial Ca(2+) uptake. Simultaneously, low mitochondrial calcium uniporter activity may also prevent mitochondrial Ca(2+) overload in such active tissues exposed to frequent cytosolic Ca(2+) activity.

Show MeSH
Related in: MedlinePlus