Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt

Stéphane Rolland , Sandra Schneid , Melanie Schwarz , Elisabeth Rackles , Christian Fischer (1) , Simon Haeussler , Saroj Regmi , Assa Yeroslaviz (2) , Bianca Habermann (3) , Dejana Mokranjac , Eric Lambie , Barbara Conradt

1 LTC - Laboratoire de Technologie des Composites et Polymères
2 MPIB - Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry
3 IBDM - Institut de Biologie du Développement de Marseille

The induction of the mitochondrial unfolded protein response (UPRmt) results in increased transcription of the gene encoding the mitochondrial chaperoneHSP70. We systematically screened the C.elegans genome and identified 171 genes that, whenknocked down, induce the expression of anhsp-6HSP70 reporter and encode mitochondrial proteins.These genes represent many, but not all, mitochondrial processes (e.g., mitochondrial calcium homeostasis and mitophagy are not represented).Knockdown of these genes leads to reduced mitochondrial membrane potential and, hence,decreased protein import into mitochondria. Inaddition, it induces UPR mtin a manner that is dependent on ATFS-1 but that is not antagonized by the kinase GCN-2. We propose that compromised mitochondrial protein import signals the induction of UPR mt and that the mitochondrial targeting sequence of ATFS-1 functions as a sensor for this signal.

Domaines: Sciences du Vivant [q-bio]; Biologie cellulaire; Organisation et fonctions cellulaires [q-bio.SC]; Bio-informatique [q-bio.QM]

Stéphane Rolland, Sandra Schneid, Melanie Schwarz, Elisabeth Rackles, Christian Fischer, et al.. Compromised Mitochondrial Protein Import Acts as a Signal for UPRmt. Cell Reports, 2019, 28 (7), pp.1659-1669.e5. ⟨10.1016/j.celrep.2019.07.049⟩. ⟨hal-02368973⟩