Mitochondria: In the Cross Fire of SARS-CoV-2 and Immunity

Abstract

The pathophysiology, immune reaction, and differential vulnerability of different population groups and viral host immune system evasion strategies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are not yet well understood. Here, we reviewed the multitude of known strategies of coronaviruses and other viruses to usurp mitochondria-associated mechanisms involved in the host innate immune response and put them in context with the current knowledge on SARS-CoV-2. We argue that maintenance of mitochondrial integrity is essential for adequate innate immune system responses and to blunt mitochondrial modulation by SARS-CoV-2. Mitochondrial health thus may determine differential vulnerabilities to SARS-CoV-2 infection rendering markers of mitochondrial functions promising potential biomarkers for SARS-CoV-2 infection risk and severity of outcome. Current knowledge gaps on our understanding of mitochondrial involvement in SARS-CoV-2 infection, lifestyle, and pharmacological strategies to improve mitochondrial integrity and potential reciprocal interactions with chronic and age-related diseases, e.g., Parkinson disease, are pointed out.

Keywords: Cell Biology; Immunology; Virology.

Graphical abstract

Figure 1

Putative Mechanisms of Mitochondria-Related Immune Functions Manipulated by SARS-CoV and SARS-CoV-2 Red rectangles represent viral proteins, whose association with mitochondrial proteins of the host cells have been shown in SARS-CoV (except for Nsp4 and ORF9c, bold, for which interaction with mitochondrial components has been suggested only for SARS-CoV-2. ORF3b is not expressed in SARS-CoV-2). ETS, electron transport system.

Figure 2

Possible Role of Mitochondrial Dysfunction in Aggravation of Hypoxemia in SARS-CoV-2 Mitochondrial dysfunction due to SARS-CoV2 infection contributes to pulmonary tissue damage, deterioration of pulmonary function, and airway hypoxia. Impaired mitochondria in the carotid bodies may worsen hypoxemia due to impaired oxygen sensing and result in a compromised chemoreflex. Oxidative stress and impaired anti-viral signaling lead to an imbalanced innate immune response.

Figure 3

Perturbance of Energy Metabolism, Mitochondrial Dynamics, and Mitochondrial Anti-viral Signaling due to SARS-Coronavirus Infection SARS-coronavirus infection is believed to induce mitochondrial dysfunction, resulting in oxidative phosphorylation (OXPHOS) deficits, the production of mtROS, dysregulated mitochondrial dynamics, and compromised mitochondrial anti-viral signaling. In combination with hypoxemia it may change cellular bioenergetics, favoring glycolysis over OXPHOS. In summary the new cellular conditions promote viral replication.