SARS-CoV-2 and mitochondrial dysfunction
Although there is a high possibility that SARS-CoV-2 might hijack host
mitochondria, it is not clear whether it suppresses its function to
escape from mitochondria-mediated immune response or whether it uses
mitochondria to establish its infection. But a possible hypothesis
proposed is SARS-CoV-2 benefits from causing mitochondrial dysfunction
for survival. Thus, it is suspected that the hijacking of host
mitochondria by SARS-CoV-2 suppresses immunity and aids in the
manipulation of mitochondrial function, including the immune pathways
involving the MAVS protein. Recent studies have shown that MAVS is
activated by the retinoic acid-inducible gene I (RIG-1), which can sense
the presence of viral RNA (Furr, Moerdyk-Schauwecker, Grdzelishvili &
Marriott, 2010; Kowalinski et al., 2011). By interacting with viperin,
an antiviral protein, MAVS is also capable of affecting interferon
levels, thereby acting as a means of antiviral defense (Hee &
Cresswell, 2017).
An understanding of mitochondrial hijacking by SARS-CoV-2 is imperative
as mitochondria are known to have various ties to the host’s immune
system. They are capable of altering signaling and metabolic pathways
and the transcription of genes within immune cells. For example, by
changing the type of respiration, the mitochondria can switch the
phenotype between pro and anti-inflammatory (Mills et al., 2016; Mills
& O’Neill, 2016). Furthermore, the virus relies on the mitochondria’s
production of energy for sustenance, which leads to the theory that
modulation of mitochondrial metabolism may prove to be an effective
method against the virus. It is also known that replication of this
virus relies on the production of double-membrane vesicles (DMVs) from
the endoplasmic reticulum (Cortese et al., 2017; Knoops et al., 2008;
Maier et al., 2013; Ulasli, Verheije, de Haan & Reggiori, 2010). The
virus replicates on the location of these DMVs and uses them to escape
the host cell’s immune defenses. It has also been theorized that
SARS-CoV-2 manipulates mitochondria through the formation of
double-membrane mitochondrial-derived vesicles (MDVs) (Singh, Chaubey,
Chen & Suravajhala, 2020; Wu, Fazal, Parker, Zou & Chang, 2020).
However, there is still no clear evidence proving MDVs promote viral
replication. Therefore, it is essential to focus on such areas to reveal
the importance of mitochondrial dysfunction and SARS-CoV-2 establishment
in the COVID-19 pathogenesis. If these hypotheses are true, improving
mitochondrial function in SARS-CoV-2 host cells could prevent or
decrease the infection or pathogenesis.