TABLE 2.

SARS-CoV-2 and mitochondrial protein interactions.

Viral proteins	Associated mitochondrial proteins	Role of mitochondrial proteins	Hypothesized interaction between viral/mitochondrial proteins	References
ORF9c, NSP7	NDUFAF1 and 2, NDUFB9	Involved in the assembly of Complex I in ETC	Dysfunctional/improper Complex I assembly, resulting in excess production of mtROS	Mimaki et al., 2012; Gordon et al., 2020
Catalytically dead NSP5	TRMT1	Performs dimethylguanosine base modification in both nuclear and mitochondrial tRNAs	Viral proteins localize TRMT1 exclusively to mitochondria, which increases ROS levels and sensitivity to oxidative stress	Dewe et al., 2017; Gordon et al., 2020
Membrane protein	ATP1B1, ATP6V1A, ACADM, AASS, PMPCB, PITRM1, PMPCA, COQ8B	Help assemble ATPase (ATP1B1 and ATP6V1A), acyl-CoA dehydrogenase (ACADM), mitochondrial processing peptidase subunit (PMPCB), and other metabolic components	Deregulation of normal mitochondrial metabolism	Gordon et al., 2020; Singh et al., 2020
ORF9b	TOMM70	Transports proteins into mitochondria and modulates anti-viral cellular defense pathways	Mutation or damage of TOMM70 is known to cause defects in oxidative phosphorylation (including elevated ROS production), and may also enable SARS-CoV-2 to suppress anti-viral response via the mitochondria	Shi et al., 2018; Gordon et al., 2020; Singh et al., 2020