Cirrincione AM et al. (2019) Exp Neurol "Analyzing chemotherapy-induced peripheral neuropathy in vivo using non-mammalian animal models."

Rieger S, Cirrincione AM

[Exp Neurol, 2019]

Non-mammalian models of CIPN remain relatively sparse, but the knowledge gained from the few published studies suggest that these species have great potential to serve as a discovery platform for new pathways and underlying genetic mechanisms of CIPN. These models permit large-scale genetic and pharmacological screening, and they are highly suitable for in vivo imaging. CIPN phenotypes described in rodents have been confirmed in those models, and conversely, genetic players leading to axon de- and regeneration under conditions of chemotherapy treatment identified in these non-mammalian species have been validated in rodents. Given the need for non-traditional approaches with which to identify new CIPN mechanisms, these models bear a strong potential due to the conservation of basic mechanisms by which chemotherapeutic agents induce neurotoxicity.

Cuong Tran H et al. (2020) Mitochondrion "Mitochondrial unfolded protein-related responses across kingdoms: similar problems, different regulators."

Cuong Tran H, Van Aken O

[Mitochondrion, 2020]

Mitochondria are key components of eukaryotic cells, so their proper functioning is monitored via different mitochondrial signalling responses. One of these mitochondria-to-nuclear 'retrograde' responses to maintain mitochondrial homeostasis is the mitochondrial unfolded protein response (UPR^mt), which can be activated by a variety of defects including blocking mitochondrial translation, respiration, protein import or transmembrane potential. Although UPR^mt was first reported in cultured mammalian cells, this signalling pathway has also been extensively studied in the nematode Caenorhabditis elegans. In yeast, there are no published studies focusing on UPR^mt in a strict sense, but other unfolded protein responses (UPR) that appear related to UPR^mt have been described, such as the UPR activated by protein mistargeting (UPR^am) and mitochondrial compromised protein import response (mitoCPR). In plants, very little is known about UPR^mt and only recently some of the regulators have been identified. In this paper, we summarise and compare the current knowledge of the UPR^mt and related responses across eukaryotic kingdoms: animals, fungi and plants. Our comparison suggests that each kingdom has evolved its own specific set of regulators, however, the functional categories represented among UPR^mt-related target genes appear to be largely overlapping. This indicates that the strategies for preserving proper mitochondrial functions are partially conserved, targeting mitochondrial chaperones, proteases, import components, dynamics and stress response, but likely also non-mitochondrial functions including growth regulators/hormone balance and amino acid metabolism. We also identify homologs of known UPR^mt regulators and responsive genes across kingdoms, which may be interesting targets for future research.