Evidence
Citations attached to nodes and edges in the mechanism map. These are placeholder records for the prototype — verify every reference before citing it.
Demo placeholder record · Demo journal record · 2019 · Original research
mouse · Primary neonatal cardiomyocytes
Placeholder record standing in for the well-described S1PR1 → Gi → MEK/ERK axis in cardiac myocytes. In a live deployment this slot is filled by verified PubMed records retrieved for the query 'S1PR1 ERK cardiomyocyte'.
Demo placeholder record · Demo journal record · 2017 · Original research
rat · L6 myotubes
Placeholder for literature describing MAPK/ERK contribution to GLUT4 translocation, which is context-dependent and partly redundant with PI3K/AKT signalling.
Demo placeholder record · Demo journal record · 2014 · Original research
mouse · Isolated soleus muscle
Placeholder for the counter-position: MEK inhibition does not block insulin-stimulated GLUT4 translocation in several models, arguing ERK is modulatory rather than required.
Demo placeholder record · Demo journal record · 2016 · Original research
mouse · Langendorff perfused heart
Placeholder for evidence that GLUT4-mediated uptake is rate-influencing for cardiac glycolytic flux under increased workload.
Demo placeholder record · Demo journal record · 2018 · Review
human · Isolated mitochondria / review
Placeholder review covering canonical TCA → NADH/FADH2 → electron transport chain → ATP synthesis coupling, and how substrate selection changes respiratory control.
Demo placeholder record · Demo journal record · 2015 · Review
other · Review
Placeholder review of complex I/III ROS production and its dependence on membrane potential and electron flux.
Demo placeholder record · Demo journal record · 2020 · Original research
mouse · In vivo ischemia-reperfusion
Placeholder for cardioprotection literature; relevant because protective phenotypes are often attributed to metabolic and mitochondrial effects that are rarely measured directly.
Demo placeholder record · Demo journal record · 2013 · Review
human · Human heart / rodent models
Placeholder for the well-documented reduction in glucose utilisation and increased fatty acid oxidation in type 2 diabetic myocardium, with reduced cardiac efficiency.
Demo placeholder record · Demo journal record · 2021 · Review
human · Endothelial and tumour cell lines
Placeholder for the sparse and mostly non-cardiac literature linking S1P receptor signalling to mitochondrial bioenergetics. This is the adjacency that makes the S1PR1 → respiration link a candidate knowledge gap.
Demo placeholder record · Demo journal record · 2022 · Original research
rat · Seahorse XF analyser
Placeholder methods reference for OCR/ECAR normalisation, seeding density and mito-stress-test interpretation in cardiac cells.
S1P
Sphingosine-1-phosphate
Glucose
Extracellular glucose
S1PR1
Sphingosine-1-phosphate receptor 1
GLUT4
Solute carrier family 2 member 4 (SLC2A4)
Gαi
Heterotrimeric G protein, inhibitory alpha subunit
RAF
RAF proto-oncogene serine/threonine kinase
MEK1/2
Mitogen-activated protein kinase kinase 1/2
ERK1/2
Extracellular signal-regulated kinase 1/2 (MAPK3/MAPK1)
AS160
TBC1D4, Akt substrate of 160 kDa
GLUT4 translocation
GLUT4 storage vesicle trafficking to the sarcolemma
Glucose uptake
Cellular glucose uptake
Glycolysis
Glycolytic pathway (ECAR readout)
Pyruvate
Pyruvate
Mitochondrial respiration
Mitochondrial respiration (OCR)
PDH
Pyruvate dehydrogenase complex
TCA cycle
Tricarboxylic acid cycle
NADH
Reduced nicotinamide adenine dinucleotide
ETC
Electron transport chain (complexes I–IV)
ΔΨm
Mitochondrial membrane potential
ATP
Adenosine triphosphate
ROS
Mitochondrial reactive oxygen species
Transcription
ERK-dependent transcriptional programme
PGC-1α
PPARGC1A, peroxisome proliferator-activated receptor gamma coactivator 1-alpha
SERCA2a
Sarco/endoplasmic reticulum Ca²⁺-ATPase 2a (ATP2A2)