Involvement of MCSs associated with ER, POs, mitochondria, and lysosomes in lipid and metabolite transfer between organelles (see Box 2 for details). MCSs between POs and other organelles (adapted from Fujiki et al. [2022]). One example of the involvement of MCS in metabolite transport comes from the yeast ERMES complex implicated in phospholipid transfer. It serves as the mitochondrial sink for unsaturated acyl chains by mediating mitochondrial transfer of di-unsaturated PS from the ER for conversion to PE, and transports PA from the ER to mitochondria for CL biosynthesis (Renne et al., 2022). It could also be involved in metabolite (possibly other glycerophospholipids) transfer between the ER, POs, and mitochondria. Another illustration is the mammalian MCS between lysosomes, POs, and the ER, involved in cholesterol transport between the lysosomes and the ER, via the POs (Chu et al., 2021; Xiao et al., 2019). Citrate is transferred from POs to mitochondria through expanded contact sites following PEX34 overexpression in yeast (Chalermwat et al., 2019). Very long chain fatty acids (VLCFA) are transported by the MCS involving VAPB and ACBD4/5 (Costello et al., 2017). VPS13D bridges the ER to mitochondria and POs via Miro (Guillén-Samander et al., 2021) and VPS13 transports bulk lipids, especially PC and PE (Kumar et al., 2018). PI4P is delivered to mitochondria to stimulate its division, either from lysosomes by lysosomal ORP1L, ER-localized VAP, and a three-way contact between the ER, lysosomes, and mitochondria (Boutry and Kim, 2021) or from Golgi-derived vesicles (König et al., 2021; not shown). The roles of other MCSs described in Box 2 remain to be clearly defined.