Sandbox Reserved 1626: Difference between revisions

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CARDIAC CYCLE PICTURE?

DEPOLARIZATION?

Ischemia/reperfusion injury (IRI) is caused by the rapid restoration of oxygen to ischemic (oxygen-deficient) tissues. In ischemic conditions, cells undergo anaerobic glycolysis. Because of the cessation of oxidative phosphorylation, the mitochondrial membrane potential is diminished. Additionally, the cytosolic pH is decreased. This drop in pH causes an increase in calcium concentration in the cytoplasm. When oxygen returns, there's a rapid restoration of membrane potential as oxidative phosphorylation resumes. This provides a strong driving force for the entry of calcium into the mitochondria which triggers mitochondrial calcium overload and cell death.<ref name="Woods" />

[https://en.wikipedia.org/wiki/Reperfusion_injury Ischemia/reperfusion injury (IRI)] is caused by the rapid restoration of oxygen to ischemic (oxygen-deficient) tissues. In ischemic conditions, cells undergo [https://en.wikipedia.org/wiki/Anaerobic_glycolysis anaerobic glycolysis]. Because of the cessation of oxidative phosphorylation, the mitochondrial membrane potential is diminished. Additionally, the cytosolic pH is decreased. This drop in pH causes an increase in calcium concentration in the cytoplasm. When oxygen returns, there's a rapid restoration of membrane potential as oxidative phosphorylation resumes. This provides a strong driving force for the entry of calcium into the mitochondria which triggers mitochondrial calcium overload and [https://en.wikipedia.org/wiki/Apoptosis cell death].<ref name="Woods" />

Therefore, certain issues with the MCU that cause an imbalance in mitochondrial calcium can lead to heart failure. Additionally, even if there is nothing wrong with the MCU, it can have an impact in conditions like IRI. This makes the MCU an interesting target for therapies for both cardiac conditions and many other ailments.

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=== Cancer ===

Cancer is another condition that can impacted by the MCU, though not much is known about the exact mechanisms. It has mostly been studied in the context of ~~breat~~ and colorectal cancers. Overexpression or overactivation of the MCU complex was shown to promote cancer proliferation. Additionally, the overexpression of MICU1 and MICU2 was shown to decrease mitochondrial calcium levels and prevent apoptosis in cancer cells.<ref name="Woods" /> Again, not much is known about the connection between the MCU and cancer cell growth, but the MCU's control over apoptosis and cell growth indicates that mitochondrial calcium regulation is fundamental to cancer cell growth and migration.

Cancer is another condition that can impacted by the MCU, though not much is known about the exact mechanisms. It has mostly been studied in the context of breast and colorectal cancers. Overexpression or overactivation of the MCU complex was shown to promote cancer proliferation. Additionally, the overexpression of MICU1 and MICU2 was shown to decrease mitochondrial calcium levels and prevent apoptosis in cancer cells.<ref name="Woods" /> Again, not much is known about the connection between the MCU and cancer cell growth, but the MCU's control over apoptosis and cell growth indicates that mitochondrial calcium regulation is fundamental to cancer cell growth and migration.

== Regulation/Inhibition ==

Sandbox Reserved 1626: Difference between revisions

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@@ Line 33: / Line 33: @@
 CARDIAC CYCLE PICTURE?
+DEPOLARIZATION?
-Ischemia/reperfusion injury (IRI) is caused by the rapid restoration of oxygen to ischemic (oxygen-deficient) tissues. In ischemic conditions, cells undergo anaerobic glycolysis. Because of the cessation of oxidative phosphorylation, the mitochondrial membrane potential is diminished.  Additionally, the cytosolic pH is decreased.  This drop in pH causes an increase in calcium concentration in the cytoplasm. When oxygen returns, there's a rapid restoration of membrane potential as oxidative phosphorylation resumes.  This provides a strong driving force for the entry of calcium into the mitochondria which triggers mitochondrial calcium overload and cell death.<ref name="Woods" />
+[https://en.wikipedia.org/wiki/Reperfusion_injury Ischemia/reperfusion injury (IRI)] is caused by the rapid restoration of oxygen to ischemic (oxygen-deficient) tissues. In ischemic conditions, cells undergo [https://en.wikipedia.org/wiki/Anaerobic_glycolysis anaerobic glycolysis]. Because of the cessation of oxidative phosphorylation, the mitochondrial membrane potential is diminished.  Additionally, the cytosolic pH is decreased.  This drop in pH causes an increase in calcium concentration in the cytoplasm. When oxygen returns, there's a rapid restoration of membrane potential as oxidative phosphorylation resumes.  This provides a strong driving force for the entry of calcium into the mitochondria which triggers mitochondrial calcium overload and [https://en.wikipedia.org/wiki/Apoptosis cell death].<ref name="Woods" />
 Therefore, certain issues with the MCU that cause an imbalance in mitochondrial calcium can lead to heart failure.  Additionally, even if there is nothing wrong with the MCU, it can have an impact in conditions like IRI.  This makes the MCU an interesting target for therapies for both cardiac conditions and many other ailments.
@@ Line 40: / Line 41: @@
 === Cancer ===
-Cancer is another condition that can impacted by the MCU, though not much is known about the exact mechanisms.  It has mostly been studied in the context of breat and colorectal cancers.  Overexpression or overactivation of the MCU complex was shown to promote cancer proliferation.  Additionally, the overexpression of MICU1 and MICU2 was shown to decrease mitochondrial calcium levels and prevent apoptosis in cancer cells.<ref name="Woods" />  Again, not much is known about the connection between the MCU and cancer cell growth, but the MCU's control over apoptosis and cell growth indicates that mitochondrial calcium regulation is fundamental to cancer cell growth and migration.
+Cancer is another condition that can impacted by the MCU, though not much is known about the exact mechanisms.  It has mostly been studied in the context of breast and colorectal cancers.  Overexpression or overactivation of the MCU complex was shown to promote cancer proliferation.  Additionally, the overexpression of MICU1 and MICU2 was shown to decrease mitochondrial calcium levels and prevent apoptosis in cancer cells.<ref name="Woods" />  Again, not much is known about the connection between the MCU and cancer cell growth, but the MCU's control over apoptosis and cell growth indicates that mitochondrial calcium regulation is fundamental to cancer cell growth and migration.
 == Regulation/Inhibition ==