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. 2021 Sep 30;22(19):10579. doi: 10.3390/ijms221910579

Figure 2.

Figure 2

Schematic drawing showing metabolic pathways, calcium cycling and implicated signaling in normal myocardium. Green arrows promote signaling or activity. Metabolic pathways on the left show that in normal heart, fatty acid (FA) metabolism and mitochondrial (mt)-FA-β-oxidation contribute 60–90%, while glucose and pyruvate metabolism contribute 10–40% of the generated adenosine triphosphate ATP by oxidative phosphorylation (OXPHOS). On the far right is a presentation of calcium cycling and its regulation by protein kinase A (PKA) signaling. Please refer to text for details. In the center of the figure is a presentation of signaling pathways modulating mt-function and metabolism. The bottom center of the figure shows the tethering complexes that exist between the endoplasmic reticulum (ER) and neighboring mitochondria and how they crosstalk via calcium signaling. The presence of mt-calcium uniporter (MCU)-independent mt-calcium uptake via the ryanodine receptor 1 (RYR1) into the mt-matrix has not been clearly validated and is represented by a question mark (?). Abbreviations: GLUT4: glucose transporter member 4, CD36: FA transporter, MPC: mt-pyruvate carrier, PDH: pyruvate dehydrogenase, TCA: tricarboxylic acid, PKCε: protein kinase C epsilon isoform, PKCδ: protein kinase C delta isoform, CaMKIIδ: calcium/calmodulin kinase delta isoform, ADP: adenosine diphosphate, MFN2: mitofusin 2, IP3: inositol triphosphate, IP3R: inositol triphosphate receptor, VDAC1: voltage dependent anion channel 1, LETM1: leucine zipper and EF-hand containing transmembrane protein 1, NCLX: sodium/calcium/lithium exchanger, ANT1: ADP/ATP translocase 1, RYR2: ryanodine receptor isoform 2, SIRT3: sirtuin 3, MICOS: mt-cristae organizing system, ETC: electron transport chain, CPT1B: carnitine-O-palmitoyltransferase 1 muscle isoform, CPT2: carnitine-O-palmitoyltransferase isoform 2, AKAP: A-kinase anchoring protein, PP2A: calcineurin, DRP-1: dynamin-related protein 1, PLN: phospholamban, SERCA2a: sarco/endoplasmic reticulum calcium ATPase isoform 2a, TNNI3: troponin I, cardiac muscle, RI and RII: regulatory unit I and II, LTCC: L-type calcium channel, NCX-1: sodium/calcium exchanger 1, GPCR: G protein-coupled receptor, PLC: phospholipase C, DAG: diacylglycerol, MAPK: mitogen-activated protein kinase, JNK: c-Jun N-terminal kinase, Bcl-2: B-cell lymphoma 2, Bax: Bcl-2 associated X, BNIP3: Bcl-2 nineteen kilodalton interacting protein 3, AMPK: adenosine monophosphate-activated protein kinase, PGC-1α: peroxisome proliferator-activated receptor gamma coactivator-1 alpha. PDE4: phosphodiesterase 4, cAMP: cyclic adenosine monophosphate, and ADCY5: adenylate cyclase type 5.