The retrograde signaling pathway

The retrograde signaling pathway. A signal from dysfunctional mitochondria is transduced by Rtg2 to the heterodimeric transcription factor Rtg1–Rtg3. The phosphatase activity of Rtg2 may partially dephosphorylate Rtg3, facilitating the translocation of Rtg1–Rtg3 into the nucleus, where it induces the expression of a wide array of retrograde response target genes. The retrograde transcription factor is aided in this gene induction by the transcriptional co-activator complex SLIK (SAGA-like), which contains Rtg2 as an integral component. The translocation of Rtg1–Rtg3 into the nucleus is inhibited by Mks1, which in a complex with the 14-3-3 proteins Bmh1/2 promotes hyperphosphorylation of Rtg3. Rtg2 can prevent this by sequestering Mks1. Mks1 is degraded by a ubiquitin-dependent mechanism, involving the ubiquitin ligase Grr1. The nutrient-sensing TORC1, one subunit of which is the WD-protein Lst8 a know retrograde response regulator, inhibits retrograde signaling both upstream and downstream of Rtg2. It negatively regulates Rtg2 and positively regulates Mks1.

Publication

The Retrograde Response: When Mitochondrial Quality Control Is Not Enough. () S. Michal Jazwinski. Biochim Biophys Acta. ;1833(2):400-409. Figure: F2. Saccharomyces cerevisiae S288C

Disease mentions