Mitochondrial Cholesterol Metabolism and Signaling in Cell Survival

Speaker:

Michelangelo Campanella, PharmD, PhD, MRPharmS, PGCAP, FHEA, PHF, FRSB 

Event date: 25 May 2023 Lausanne, Switzerland 

Mitochondria have active roles in remodelling and reprogramming of mammalian cells to evade demise. In response to endogenous and exogenous stressors, mitochondria retro-communicate with the nucleus to induce wide-ranging cytoprotective effects, via gene expression, that sustain cell survival and proliferation. This process, called mitochondrial retrograde response (MRR), is exploited in diseases characterized by sustained growth (e.g., cancer). 

In hormone-derived cancers, such as those of the mammary gland, cholesterol is pivotal to MRR by forming lipid-rich sites of contact which couple mitochondria and nucleus to expedite communication between the organelles. Cholesterol redistribution due to impaired mitochondrial function represents a target to use as a biomarker, as well as a therapeutic target to counteract uncontrolled and pathological cells proliferation. 

Evidence is presented from studies in canine cells in which mishandling of cholesterol and increased mitochondrial retrograde signaling with the nucleus emerge as pathophysiological traits in canine mammary tumors.