The role of mitochondrial dynamics in triple negative breast cancer

Triple-negative breast cancer, the most aggressive subtype with the worst prognosis, lacks targeted therapies and often leads to rapid metastasis. Dynamic changes in mitochondrial shape, regulated by dynamin family GTPases, significantly impact tumor initiation and progression, including cell growth, energy production, cell death, and mobility. The interplay between mitochondrial morphology and metabolism is crucial, with nutrient availability and metabolic demands influencing whether mitochondria become fragmented or hypertubular. Furthermore, alterations in mitochondrial dynamics components can trigger metabolic changes, highlighting the importance of active mitochondrial dynamics in metabolic adaptation. The current scientific literature remains inconclusive regarding the precise influence and mechanisms by which mitochondrial dynamics impact breast cancer progression. For this reason, we undertook a comprehensive investigation into mitochondrial morphology using an isogenic model of human breast cancer progression, ranging from normal breast cells to malignant, utilizing advanced high-throughput imaging technologies. Additionally, we sought to unravel the influence of different energy sources on mitochondrial shape through a similar approach. To gain insights into the role of key proteins involved in mitochondrial dynamics in the progression of triple-negative breast cancer, we conducted experiments involving their silencing, followed by detailed analyses of major breast cancer hallmarks like proliferation, migration, and cells survival.