Review Article

Functions of BCL-XL at the Interface between Cell Death and Metabolism

Table 1

Functions of BCL-XL at the interface between cell death regulation and other aspects of the cell biology.

InteractorMain localizationNotes(s)Reference

BADCytosol
mitochondria
By antagonizing BAD, BCL-XL modulates the metabolic functions of a
mitochondrial multiprotein complex involving glucokinase, PKA, and PP1
[64]
Beclin 1Cytosol
Golgi network
BCL-XL binds to Beclin 1, thus inhibiting stress-induced, 
but not baseline, autophagy
[94, 97, 100]
DRP1MitochondriaBCL-XL interacts with DRP1, altering the mitochondrial 
function of neurons to stimulate the formation of synapses
[117]
F1FO ATP
synthase
MitochondriaBCL-XL increases the enzymatic activity of the F1FO ATP synthase, hence,
stabilizing the and maximizing mitochondrial ATP synthesis
[67, 68]
IP3RERBCL-XL reduces Ca2+ concentration in the ER[2527]
Krebs’s cycleMitochondriaBCL-XL overexpression reduces the levels of virtually all TCA (but not
glycolytic) intermediates, modulating both N- -acetylation and autophagy
[74, 7982]
MAPK9
PLK1
Cytosol
nucleus
BCL-XL is phosphorylated at S49 by PLK1 and 
MAPK9 in a cell cycle-dependent fashion
[104]
NLRP1
inflammasome
CytosolBCL-XL inhibits the NLRP1 inflammasome, 
interfering with the secretion of IL-1 and IL-18
[118, 120]
p53Cytosol
mitochondria
BCL-XL binds to p53, hence, inhibiting both 
its pro-apoptotic and metabolic functions
[54, 60, 66]
PKM2Cytosol
mitochondria
PKM2 stimulates the expression of BCL-XL at the transcriptional level[78]
PLK3Cytosol
nucleus
PLK3 phosphorylates BCL-XL at S62 in response to DNA-damaging 
agents, favoring a cell cycle arrest at the G2 checkpoint
[105]
RAC2Cytosol
plasma membrane
In some settings, antiapoptotic BCL-2 family members exert prooxidant
functions, perhaps linked to their interaction with RAC2
[7072]
VDAC1MitochondriaBCL-XL promotes the exchange of metabolites 
between the cytosol and the mitochondrial matrix
[24, 44]

: mitochondrial transmembrane potential; DRP: dynamin-related protein 1; ER: endoplasmic reticulum; IL: interleukin; IP3R: inositol 1,4,5-triphosphate receptor; MAPK9: mitogen-activated protein kinase 9; PKA: protein kinase A; PKM2: pyruvate kinase M2; PLK: polo-like kinase 1; PP1: protein phosphatase 1; VDAC1: voltage-dependent anion channel 1.