Oxidative Medicine and Cellular Longevity

Review Article

Mitochondria-Endoplasmic Reticulum Contacts: The Promising Regulators in Diabetic Cardiomyopathy

Table 1

Summary of the functional MAMs proteins.


Functions	MAMs proteins	Relevant functions in MAMs	Reference

Ca²⁺ transfer	IP3R1/2/3	Interacts with VDAC via GRP75, a major actor in ER Ca²⁺ release to mitochondria	[22]
	VDAC1	Acts as a Ca²⁺ uptake channel in the OMM	[22]
	GRP75	Chaperone protein connects IP3R and VDAC to form VDAC1/GRP75/IP3R1 channel complex	[22]
	PTPIP51	Interacts with VAPB at MAMs and regulates Ca²⁺ homeostasis	[24]
	VAPB	Interacts with PTPIP51 at MAMs and regulates Ca²⁺ homeostasis	[24]
	SERCA	Acts as an important pump involved in Ca²⁺ transport into ER	[33]
	Sig-1R	Generates a chaperone complex with BiP/GRP78 and prolongs Ca²⁺ signaling stabilizing subunit 3 of IP3R	[105]
	P53	Regulates SERCA activity and modulates ER-mitochondrial transfer	[106]
	PML	Regulates Ca²⁺ transfer and control apoptosis	[29]
	Calnexin	Interacts with SERCA, regulating Ca²⁺ transfer between contact sites	[107]
	Cytc	Interacts with IP3Rs and regulate Ca²⁺	[108]
	Bcl-2	Inhibit the opening of IP3Rs and downregulate IP3R-mediated Ca²⁺ flux	[109]
	CYPD	A partner of the IP3R1-GRP75-VDAC1 complex and changes the MAM spatial structure	[30]
	mTORC2	Regulates Ca²⁺ signaling by Akt regulation	[110]
	PP2A	Recruited by PML and inactivates AKT, facilitates IP3R-mediated Ca²⁺ release	[29]
	PTEN	PTEN regulates ER Ca2+ release through type 3 IP3R in a protein phosphatase-dependent manner	[111]
	Akt	Akt phosphorylates all IP3R isoforms and inhibits Ca²⁺ release from the ER	[38]
	GSK3β	Regulates organelle Ca²⁺ exchange	[37]
	FUNDC1	Binding of FUNDC1 to IP3R2 at the MAMs increases the Ca²⁺ concentration in both cytosol and mitochondrial matrix	[26]
	MFN2	Forms dimers with either MFN1 or MFN2 located on the mitochondria, controls the mitochondrial fusion	[23]
Mitochondrial dynamics	Bax	Interacts with MFN2 to promote mitochondrial fusion	[112]
	FUNDC1	Interacts with OPA1 to promote mitochondrial fusion; promote mitochondrial fission under hypoxic condition	[46]
	DRP1	Regulates mitochondrial fission	[18]
	INF2	Drives initial mitochondrial constriction	[50]
	MFF	Recruits DRP1 and regulates mitochondrial fission	[113]
	FIS1	Recruits DRP1 and regulates mitochondrial fission	[114]
	MiD49/51	Recruits DRP1 and regulates mitochondrial fission	[55]
Autophagy	ATG14L	Acts as preautophagosome marker, induces autophagosome formation	[59]
	ATG5	Acts as autophagosome marker	[59]
	PACS2	Knocking down PACS2 decreases the number of autophagosomes	[115]
	MFN2	Knocking down MFN2 decreases the number of autophagosomes	[115]
	VAPB	Regulates autophagy	[24]
	PTPIP51	Forms a complex with VAPB to regulate autophagy	[24]
	BECLIN1	Enhances the formation of MAMs and autophagosomes	[60]
	PINK1	Promote ER-mitochondrial tethering and autophagosome formation	[60]
Inflammation	NLRP3	NLRP3 inflammasome can be recruited to the MAM sites to sense mitochondrial damage	[70]
	ASC	The adaptor of NLRP3	[70]
	TXNIP	TXNIP activates NRLP3 inflammasome activation under mitochondrial oxidative stress conditions	[116]
ER stress	PERK	Induces apoptosis after ROS-based ER stress	[117]
	IRE1α	Responses to UPR stimulation; IRE1α ubiquitylation at MAM hinder ER-stress-induced apoptosis	[118]
	MFN2	Interacts with PERK and repress its activity	[78]