Sandbox Reserved 1626: Difference between revisions

Line 41:

The most well-known and commonly used inhibitor of the MCU is [https://en.wikipedia.org/wiki/Ruthenium_red ruthenium red] (RuRed).<ref name="Woods"/> RuRed is a trinuclear, oxo-bridged complex that effectively inhibits calcium uptake without affecting mitochondrial respiration or calcium efflux.<ref name="Woods"/> The disadvantage of ruthenium red is its challenging purification.<ref name="Woods"/> Interestingly, an impure version of RuRed, termed [https://en.wikipedia.org/wiki/Ru360 Ru360], was found to be the active component of RuRed and thus another good inhibitor of the MCU.<ref name="Woods"/> Ru360 is a binuclear, oxo-bridged complex with a similar structure to that of RuRed.<ref name="Woods"/> The only flaw with Ru360 was that it showed low cell permeability, so Ru265 was developed and had twice the cell permeability of Ru360.<ref name="Woods"/> Ru265 possesses two bridged Ru centers bridged by a nitride ligand.<ref name="Woods"/>

Recent experiments suggest that Ru360 inhibits calcium uptake through interactions with the WDXXEP motif.<ref name="Woods"/> However, not much is actually known about the method of inhibition. Mutations of Asp261 and Ser259 in human MCU (analogous to ~~''''~~Asp225~~'''~~ and '''Ser223''' in ''C. europaea'') were shown to maintain calcium uptake into the matrix, but reduce the inhibitory effect of Ru360.<ref name="Woods"/> Curiously, the same Ser259 mutation did not affect inhibition of Ru265.<ref name="Woods"/> Additionally, a mutation in a cysteine residue in the NTD reduced the inhibitory effects of Ru265, but not Ru360.<ref name="Woods"/> So, while various inhibitors for the MCU are known, the mechanism of each is still largely unknown.

Recent experiments suggest that Ru360 inhibits calcium uptake through interactions with the WDXXEP motif.<ref name="Woods"/> However, not much is actually known about the method of inhibition. Mutations of Asp261 and Ser259 in human MCU (analogous to Asp225 and '''Ser223''' in ''C. europaea'') were shown to maintain calcium uptake into the matrix, but reduce the inhibitory effect of Ru360.<ref name="Woods"/> Curiously, the same Ser259 mutation did not affect inhibition of Ru265.<ref name="Woods"/> Additionally, a mutation in a cysteine residue in the NTD reduced the inhibitory effects of Ru265, but not Ru360.<ref name="Woods"/> So, while various inhibitors for the MCU are known, the mechanism of each is still largely unknown.

==Medical Relevance==

Sandbox Reserved 1626: Difference between revisions

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 41: / Line 41: @@
 The most well-known and commonly used inhibitor of the MCU is [https://en.wikipedia.org/wiki/Ruthenium_red ruthenium red] (RuRed).<ref name="Woods"/>  RuRed is a trinuclear, oxo-bridged complex that effectively inhibits calcium uptake without affecting mitochondrial respiration or calcium efflux.<ref name="Woods"/>  The disadvantage of ruthenium red is its challenging purification.<ref name="Woods"/> Interestingly, an impure version of RuRed, termed [https://en.wikipedia.org/wiki/Ru360 Ru360], was found to be the active component of RuRed and thus another good inhibitor of the MCU.<ref name="Woods"/> Ru360 is a binuclear, oxo-bridged complex with a similar structure to that of RuRed.<ref name="Woods"/> The only flaw with Ru360 was that it showed low cell permeability, so Ru265 was developed and had twice the cell permeability of Ru360.<ref name="Woods"/> Ru265 possesses two bridged Ru centers bridged by a nitride ligand.<ref name="Woods"/>
-Recent experiments suggest that Ru360 inhibits calcium uptake through interactions with the WDXXEP motif.<ref name="Woods"/> However, not much is actually known about the method of inhibition. Mutations of Asp261 and Ser259 in human MCU (analogous to ''''Asp225''' and '''Ser223''' in ''C. europaea'') were shown to maintain calcium uptake into the matrix, but reduce the inhibitory effect of Ru360.<ref name="Woods"/> Curiously, the same Ser259 mutation did not affect inhibition of Ru265.<ref name="Woods"/>  Additionally, a mutation in a cysteine residue in the NTD reduced the inhibitory effects of Ru265, but not Ru360.<ref name="Woods"/> So, while various inhibitors for the MCU are known, the mechanism of each is still largely unknown.
+Recent experiments suggest that Ru360 inhibits calcium uptake through interactions with the WDXXEP motif.<ref name="Woods"/> However, not much is actually known about the method of inhibition. Mutations of Asp261 and Ser259 in human MCU (analogous to Asp225 and '''Ser223''' in ''C. europaea'') were shown to maintain calcium uptake into the matrix, but reduce the inhibitory effect of Ru360.<ref name="Woods"/> Curiously, the same Ser259 mutation did not affect inhibition of Ru265.<ref name="Woods"/>  Additionally, a mutation in a cysteine residue in the NTD reduced the inhibitory effects of Ru265, but not Ru360.<ref name="Woods"/> So, while various inhibitors for the MCU are known, the mechanism of each is still largely unknown.
 ==Medical Relevance==