Fatty acid metabolism and
steroid biosynthesis are 2 major pathways shared by peroxisomes and mitochondria. Both organelles are in close apposition to the endoplasmic reticulum, with which they communicate via interorganelle membrane contact sites to promote cellular signaling and the exchange of
ions and
lipids. To date, no convincing evidence of the direct contact between peroxisomes and mitochondria was reported in mammalian cells.
Hormone-induced, tightly controlled
steroid hormone biosynthesis requires interorganelle interactions. Using immunofluorescent staining and live-cell imaging, we found that dibutyryl-cAMP treatment of MA-10 mouse
tumor Leydig cells rapidly induces peroxisomes to approach mitochondria and form peroxisome-mitochondrial contact sites/fusion, revealed by the subcellular distribution of the endogenous
acyl-coenzyme A-binding domain (ACBD)2/ECI2
isoform A generated by alternative splicing, and further validated using a proximity
ligation assay. This event occurs likely via a peroxisome-like structure, which is mediated by peroxisomal and mitochondrial matrix
protein import complexes: peroxisomal import receptor
peroxisomal biogenesis factor 5 (PEX5), and the mitochondrial import receptor subunit translocase of outer mitochondrial membrane 20 homolog (yeast)
protein. Similar results were obtained using the mLTC-1 mouse
tumor Leydig cells. Ectopic expression of the ACBD2/ECI2
isoform A in MA-10 cells led to increased basal and
hormone-stimulated
steroid formation, indicating that ACBD2/ECI2-mediated peroxisomes-mitochondria interactions favor in the exchange of metabolites and/or macromolecules between these 2 organelles in support of
steroid biosynthesis. Considering the widespread occurrence of the ACBD2/ECI2
protein, we propose that this
protein might serve as a tool to assist in understanding the contact between peroxisomes and mitochondria.