Mitofusin 2-containing Mitochondrial-Reticular Microdomains Direct Rapid Cardiomyocyte Bioenergetic Responses via Inter-Organelle Ca2+ Crosstalk

摘要

RationaleMitochondrial Ca²⁺ uptake is essential for the bioenergetic feedback response through stimulation of Krebs cycle dehydrogenases. Close association of mitochondria to the sarcoplasmic reticulum (SR) may explain efficient mitochondrial Ca²⁺ uptake despite low Ca²⁺ affinity of the mitochondrial Ca²⁺ uniporter. However, the existence of such mitochondrial Ca²⁺ microdomains and their functional role are presently unresolved. Mitofusin (Mfn) 1 and 2 mediate mitochondrial outer membrane fusion, while Mfn2, but not Mfn1, tethers endoplasmic reticulum to mitochondria in non-cardiac cells.