Lipidated COVID-19 Localizes into Mitochondria and Causes Oxidative Damage to Mitochondrial DNA–Pathophysiology of long COVID

Protein lipidation modifies proteins in eukaryotic cells, including cysteine prenylation, and N-terminal glycine myristoylation, and regulates many biological pathways. We summarize the history of lipidation and the roles of prenylation, myristoylation, and palmitoylation. Lipidation modifies other molecules and takes them to the cellular membrane. Lipidized proteins also go to mitochondria. Prenylation links protein C end motif, and myristoylation links protein N end motif. Palmitoylation links protein C or N motif. It is possible to take both prenylation and myristoylation. Previously, we showed that HSP47 interacts with prenylated and myristoylated proteins, goes to mitochondria, and generates reactive oxygen species (ROS) from mitochondria. It is known that mitochondrial ROS (mtROS) further causes apoptosis and intra-mitochondrial damage to lipids, proteins, and mtDNA. Viral proteins are lipid-modified by infected cells and go to mitochondria, and the electron transport chain (ETC) generates further reactive oxygen species (ROS). The excess ROS may cause lipid peroxidation and damage to mitochondrial DNA (mtDNA). COVID-19, also prenylated and myristoylated, goes to mitochondria, generates mtROS, and damages mtDNA. It is the pathophysiology of long COVID.