Cardiometabolic disease (CMD) describes a group of illnesses that, together, are the number one cause of death worldwide. CMDs include obesity, heart disease, high blood pressure, diabetes, kidney disease, and unhealthy cholesterol levels. CMDs are are mainly caused by an unhealthy lifestyle, particularly smoking, lack of exercise, and/or an unhealthy diet; but a person's genetics can also directly impact disease severity.
While mitochondria are indeed responsible for generating almost all of our cells' energy, they are also responsible for many other functions including calcium homeostasis, generating body heat and signalling molecules, coordinating the recycling of damaged cells, initiating cell death, sensing changes in environmental oxygen, and mediating cell division. Mitochondria also have their own DNA - a smaller genome, passed on to all offspring by mothers only, that contains a record of prehistoric human migration out of Africa.
While CMDs have reached epidemic levels around the world, some people are more sick than others, even after controlling for age, sex, socioeconomic status, access to healthcare, etc. and the pattern of this differential disease susceptibility matches that of mitochondrial genetic ancestry. This genetic link, coupled with the links between energy production and the mitochondria, make these organelles a likely key player in the pathogenesis of CMDs.
Mitochondria are known to be a master regulator of metabolism, but the mechanisms by which some people with the same risk factors have poorer CMD prognosis is not known. At MitoMetabLab, we are investigating the links between mitochondrial genetics, mitochondrial dynamics (the shape/structure of the mitochondria in different tissues), metabolomics - large-scale studies of small molecules that are the products of caloric intake (metabolites), and the cell signalling pathways that control proliferation (cell growth). We use preclinical models of CMDs and patients with differing mitochondrial genetic ancestry to elucidate how these key players are linked. Our longterm goal is to identify circulating biomarkers of CMD and develop a mitochondrial-metabolomic fingerprint for CMDs that can be deployed in the clinic. Using this interdisciplinary approach, we strive to i) improve early intervention for subpopulations at increased risk for CMDs; ii) identify new therapeutic targets to ease the current healthcare burden; and iii) provide new tools to advance the initiative of precision/personalized medicine.