Mitochondrial Dysfunction: A Prelude to Neuropathogenesis of SARS-CoV-2

The SARS-CoV-2 virus is notorious for its neuroinvasive capability, causing multiple neurological conditions. The neuropathology of SARS-CoV-2 is increasingly attributed to mitochondrial dysfunction of brain microglia cells. However, the changes in biochemical content of mitochondria that drive the progression of neuro-COVID remain poorly understood. Here we introduce a Raman microspectrometry approach that enables the molecular profiling of single cellular organelles to characterize the mitochondrial molecular makeup in the infected microglia cells. We found that microglia treated with either spike protein or heatinactivated SARS-CoV-2 trigger a dramatic reduction in mtDNA content and an increase in phospholipid saturation levels. At the same time, no significant changes were detected in Golgi apparatus and in lipid droplets, the organelles that accommodate biogenesis and storage of lipids. We hypothesize that transformations in mitochondria are caused by increased synthesis of reactive oxygen species in these organelles. Our findings call for the development of mitochondria-targeted therapeutic approaches to limit neuropathology associated with SARS-CoV-2.

Automated summary

The SARS-CoV-2 virus can cause neurological conditions by invading the nervous system. The dysfunction of mitochondria in brain microglia cells is believed to play a role in the neuropathology of SARS-CoV-2. Using Raman microspectrometry, researchers found that infected microglia cells exhibited reduced mtDNA content and increased phospholipid saturation levels in mitochondria. These changes may be linked to increased synthesis of reactive oxygen species in the organelles.