Multi-localized proteins: the peroxisome-mitochondria connection

This is the author accepted manuscript. The final version is available from Springer via the link in this recordPeroxisomes and mitochondria are dynamic, multifunctional organelles that play pivotal cooperative roles in the metabolism of cellular lipids and reactive oxygen species. Their functional interplay, the “peroxisome-mitochondria connection”, also includes cooperation in anti-viral signalling and defence, as well as coordinated biogenesis by sharing key division proteins. In this review, we focus on multi-localised proteins which are shared by peroxisomes and mitochondria in mammals. We first outline the targeting and sharing of matrix proteins which are involved in metabolic cooperation. Next, we discuss shared components of peroxisomal and mitochondrial dynamics and division, and we present novel insights into the dual targeting of tail-anchored membrane proteins. Finally, we provide an overview of what is currently known about the role of shared membrane proteins in disease. What emerges is that sharing of proteins between these two organelles plays a key role in their cooperative functions which, based on new findings, may be more extensive than originally envisaged. Gaining a better insight into organelle interplay and the targeting of shared proteins is pivotal to understanding how organelle cooperation contributes to human health and disease.This work was supported by the Biotechnology and Biological Sciences Research Council (BB/K006231/1, BB/N01541X/1 to M.S.). M.I. is supported by the German Research Foundation (DFG 397476530) and MEAMEDMA Anschubförderung, Medical Faculty Mannheim, University of Heidelberg. J.P. is supported by CLES, University of Exeter