Cross-species screening platforms identify EPS-8 as a critical link for mitochondrial stress and actin stabilization.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34714674.
- Also identified by DOI 10.1126/sciadv.abj6818 and PMC identifier 8555897.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The dysfunction of mitochondria is associated with the physiological consequences of aging and many age-related diseases. Therefore, critical quality control mechanisms exist to protect mitochondrial functions, including the unfolded protein response of the mitochondria (UPR<sup>MT</sup>). However, it is still unclear how UPR<sup>MT</sup> is regulated in mammals with mechanistic discrepancies between previous studies. Here, we reasoned that a study of conserved mechanisms could provide a uniquely powerful way to reveal previously uncharacterized components of the mammalian UPR<sup>MT</sup>. We performed cross-species comparison of genetic requirements for survival under—and in response to—mitochondrial stress between karyotypically normal human stem cells and the nematode <i>Caenorhabditis elegans</i>. We identified a role for EPS-8/EPS8 (epidermal growth factor receptor pathway substrate 8), a signaling protein adaptor, in general mitochondrial homeostasis and UPR<sup>MT</sup> regulation through integrin-mediated remodeling of the actin cytoskeleton. This study also highlights the use of cross-species comparisons in genetic screens to interrogate cellular pathways.