The ER-SURF pathway uses ER-mitochondria contact sites for protein targeting to mitochondria

Abstract

Most mitochondrial proteins are synthesized on cytosolic ribosomes and imported into mitochondria in a post-translational reaction. Mitochondrial precursor proteins which use the ER-SURF pathway employ the surface of the endoplasmic reticulum (ER) as an important sorting platform. How they reach the mitochondrial import machinery from the ER is not known. Here we show that mitochondrial contact sites play a crucial role in the ER-to-mitochondria transfer of precursor proteins. The ER mitochondria encounter structure (ERMES) and Tom70, together with Djp1 and Lam6, are part of two parallel and partially redundant ER-to-mitochondria delivery routes. When ER-to-mitochondria transfer is prevented by loss of these two contact sites, many precursors of mitochondrial inner membrane proteins are left stranded on the ER membrane, resulting in mitochondrial dysfunction. Our observations support an active role of the ER in mitochondrial protein biogenesis.

Tissue‐specific differences in Ca2+ sensitivity of the mitochondrial permeability transition pore (PTP). Experiments in male rat liver and heart

“…In isolated mitochondria, it is not possible to collect information on activity modulation by surrounding organelles or by the differences of irrigation and hormone concentrations in the cytoplasm (Hoek et al., 1997 ; King et al., 2024 ). Still, isolated mitochondria are needed to elucidate specific catalytic mechanisms in mitochondrial proteins (Horten et al., 2024 ; Koch et al., 2024 ). In addition, some substrates and inhibitors do not traverse the plasma membrane readily and thus tight control of in‐situ mitochondrial activities is harder to achieve (Azimzadeh et al., 2016 ; Picard et al., 2011 ).…”