Preliminary investigations on the role of Drp-1 dependent mitochondrial fission in attenuating RLR downstream signaling during nervous necrosis virus infection

Abstract

Member of the dynamin family of large GTPases, dynamin-related protein 1 (Drp1) dependent mitochondrial fission is an intricate process regulating both cellular and organ dynamics. Present study shows that NNV perturbs mitochondrial dynamics by promoting Drp-1 dependent mitochondrial fission, which attenuates MAVS mediated downstream signaling. NNV infected SISS cells revealed induction in Drp1 expression and subsequent translocation into mitochondria. The level of MAVS expression was up-regulated over a period of 24 hpi and declined with the progression of NNV infection at 48 and 72 hpi confirmed by western blot and mRNA transcript analysis. Drp-1 displayed its association with fragmented mitochondria and the transcript abundance was significant post infection along with Mff. Expression levels of IRF-3 IFN-1 and Mx followed a similar pattern with abundant expression at 48 hpi and diminished expression during the further period. Importantly, silencing of Drp1 caused significant elevation in the RLR downstream molecules and reduction in viral RNA expression. These results suggest that NNV-induced mitochondrial fission serve to attenuate host RLR signaling. This provides an illustration of host-pathogen interaction in which the virus evades innate immunity by enhancing mitochondrial fission and perturbs MAVS, and the downstream molecules.

Structural Analysis of Mitochondrial Dynamics—From Cardiomyocytes to Osteoblasts: A Critical Review

“…Two important phosphorylation sites are ser616 and ser637. While phosphorylation at ser637 keeps Drp1 in the cytoplasm, phosphorylation at ser616 promotes the translocation to mitochondria [42,43]. Drp1 not only targets mitochondria but also peroxisomes and the endoplasmic reticulum [5].…”

Mitochondrial Dynamics Imbalance: A Strategy for Promoting Viral Infection

“…The translocation and function of Drp1 depend on the regulation of post-translational modification and the most common modification is phosphorylation. There are two important phosphorylation sites in Drp1, ser616, and ser637 (amino acid numbering corresponds to human Drp1), and it is also a target for many viruses to regulate mitochondrial fission activity ( Keck et al, 2017 ; Krishnan et al, 2018 ). Generally, Drp1 phosphorylation at S616 promotes its translocation into mitochondria, while phosphorylation at S637 keeps it in the cytoplasm ( Naoko et al, 2007 ).…”