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. Author manuscript; available in PMC: 2021 Dec 1.
Published in final edited form as: Mech Ageing Dev. 2020 Oct 9;192:111380. doi: 10.1016/j.mad.2020.111380

Figure 1: Schematic of mitochondrial defect in the aged hearts.

Figure 1:

Mitochondria and ER are closely connected through MAM (mitochondria associated membranes). ER stress leads to increased cytosolic calpain1 and 2 (csCPN1/2) activities that cleave beclin1 and Atg7 (autophagy protein 7). The decreased contents of beclin1 and Atg7 impair autophagosome formation that decreases mitophagy. ER stress-induced mitochondrial calcium overload activates mitochondrial calpain 1 and 2 (mCPN1/2) that leads to the degradation of metabolic enzymes and protein subunits of the respiratory complexes. The damaged individual complexes including complex I (CI), III (CIII), and IV (CIV) result in the disruption of supercomplexes. Calcium overload also triggers MPTP opening in aged heat mitochondria. (OMM, mitochondrial outer membrane; IMM, mitochondrial inner membrane; IMS, intermembrane space).