Many aerobic organisms encounter oxygen-deprived environments and thus must have adaptive mechanisms to survive such stress. It is important to understand how mitochondria respond to oxygen deprivation given the critical role they play in using oxygen to generate cellular energy. Here we examine mitochondrial stress response in C. elegans, which adapt to extreme oxygen deprivation (anoxia, less than 0.1% oxygen) by entering into a reversible suspended animation state of locomotory arrest. We show that neuronal mitochondria undergo DRP-1-dependent fission in response to anoxia and undergo refusion upon reoxygenation. The hypoxia response pathway, including EGL-9 and HIF-1, is not required for anoxia-induced fission, but does regulate mitochondrial reconstitution during reoxygenation. Mutants for egl-9 exhibit a rapid refusion of mitochondria and a rapid behavioral recovery from suspended animation during reoxygenation; both phenotypes require HIF-1. Mitochondria are significantly larger in egl-9 mutants after reoxygenation, a phenotype similar to stress-induced mitochondria hyperfusion (SIMH). Anoxia results in mitochondrial oxidative stress, and the oxidative response factor SKN-1/Nrf is required for both rapid mitochondrial refusion and rapid behavioral recovery during reoxygenation. In response to anoxia, SKN-1 promotes the expression of the mitochondrial resident protein Stomatin-like 1 (STL-1), which helps facilitate mitochondrial dynamics following anoxia. Our results suggest the existence of a conserved anoxic stress response involving changes in mitochondrial fission and fusion.
Highlights
CoVID-19 has impacted all aspects of urologic oncology, including resident and fellow training
Integration of virtual learning and telemedicine offer new opportunities and challenges
New collaborative research opportunities have arisen
Current best practices must be assessed so the field can be better prepared for future public health crises
The SUO has an opportunity to play a leading role in adapting trainee education
The Coronavirus Disease 2019 pandemic placed urologic surgeons, and especially urologic oncologists, in an unprecedented situation. Providers and healthcare systems were forced to rapidly create triage schemas in order to preserve resources and reduce potential viral transmission while continuing to provide care for patients. We reviewed United States and international triage proposals from professional societies, peer-reviewed publications, and publicly available institutional guidelines to identify common themes and critical differences. To date, there are varying levels of agreement on the optimal triaging of urologic oncology cases. As the need to preserve resources and prevent viral transmission grows, prioritizing only high priority surgical cases is paramount. A similar approach to prioritization will also be needed as nonemergent cases are allowed to proceed in the coming weeks. While these decisions will often be made on a case-by-case basis, more nuanced surgeon-driven consensus guidelines are needed for the near future.
The novel coronavirus (COVID-19) pandemic has created many unique challenges in urology resident training. Urologists are operating at a fraction of normal volume to conserve personal protective equipment and prevent viral spread. Many residency programs have organized rotating skeleton crews to perform clinical duties while a portion of residents work from home. In some regions, urology residents have been deployed to emergency rooms, intensive care units, and medical floors to care for COVID-19 patients. With these interruptions in urologic education, many questions remain about how residents will proceed with their clinical and didactic training. During these unprecedented times, many residencies have transitioned their didactic sessions to video-based platforms, allowing educators to reach larger numbers of learners. This perspective addresses how innovative virtual education programs created during the pandemic can be developed into a national video-based curriculum for urology residents, incorporating both didactics and surgical skill training.
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