TABLE 1.

Role of ceramides and S1P in mitochondrial pathways.

SL species	Pathway	Sphingolipid Level(s)
Ceramides	ETC	• $\downarrow$ CI activity with C2-ceramide Gudz et al. (1997) • $\uparrow$ CIV activity with C2-ceramide Di Paola et al. (2000) • $\downarrow$ CIV activity with C16-ceramide Di Paola et al. (2000); Zigdon et al. (2013) • $\downarrow$ CIV activity in CerS2-deficient mice Zigdon et al. (2013)
	ROS production	• $\uparrow$ ROS production with C16-ceramide Di Paola et al., (2000); Zigdon et al. (2013) • $\downarrow$ ROS production with C2 and C6-ceramides Gudz et al. (1997); Di Paola et al. (2000)
	MOMP	• $\downarrow$ MOMP with C8-ceramide Arora et al. (1997) • $\uparrow$ Mitochondrial membrane permeability transition with C2, C6, C8-ceramides Arora et al. (1997) • $\downarrow$ MOMP by ceramide induced formation of pores within the mitochondrial membrane Siskind and Colombini. (2000) • $\downarrow$ MOMP by internalization of ceramide platforms in plasma membrane and the exchange of ceramides between plasma membrane and mitochondria Babiychuk et al. (2011)
	ATP production	• $\downarrow$ ATP production with C8-ceramide Arora et al. (1997)
	Mitophagy	• $\uparrow$ Mitophagy with CerS1 derived C18-ceramide Jiang and Ogretmen. (2013) • CerS6 derived C16-ceramide interacts with mitochondrial fission factor Hammerschmidt et al. (2019) • C18 ceramide interaction with LC3B Sentelle et al. (2012) • $\uparrow$ Mitophagy involving the recruitment of LC3B-containing autophagosomes by mitochondrial ceramide Sentelle et al. (2012); Jiang and Ogretmen. (2013)
	Mitochondrial dynamics	• CerS6 derived C16-ceramide interacts with mitochondrial fission factor Hammerschmidt et al. (2019) • Ceramides can interact with VDAC2 Dadsena et al. (2019)
S1P	Mitochondrial Biogenesis	• Direct regulation via PPARγ, PGC1α Moon et al. (2012); Chen et al. (2016); Liu et al. (2016); Luo et al. (2016); Weske et al. (2018); Meyer Zu Reckendorf et al. (2020) • Indirect regulation via TFAM, NRF1, ERK, MAPK, AMPK, p38 Stechschulte et al. (2014); Banks et al. (2015); Dennhardt et al. (2019) • $\uparrow$ Mitochondrial biogenesis with S1P via S1PR2 Shen et al. (2014)
	ATP Production	• $\uparrow$ ATP production with S1P via S1PR2 Shen et al. (2014)
	ROS production	• $\uparrow$ ROS production with activation of S1P signaling Yu et al. (2018); Botta et al. (2019); Liu and Tie. (2019); Botta et al. (2020) • $\downarrow$ ROS production with inhibition of S1P signaling Pyszko and Strosznajder. (2014); Sivasubramanian et al. (2015); Oancea-Castillo et al. (2017) • $\uparrow$ ROS production with activation of S1P signaling Golan et al. (2012); Kim et al. (2014); Lin et al. (2016); Ha et al. (2020); Li et al. (2020)
	Ca2+ Homeostasis	• $\uparrow$ Mitochondrial Ca2+ with overexpression of SK1 Pulli et al. (2019) • $\downarrow$ Mitochondrial Ca2+ with exogenous S1P Agudo-Lopez et al. (2010)
	Mitochondrial dynamics	• $\uparrow$ DRP1 with exogenous S1P via S1PR3 Brand et al. (2018) • $\downarrow$ DRP1 with inhibition of S1P via S1PR2 Chen et al. (2019) • $\downarrow$ OPA1 and MFN1 with SK inhibitor Hong et al. (2018) • Altering the expression of S1PR1 perturbed the equilibrium of gene expression related to mitochondrial fission and fusion Bajwa et al. (2015)