This review article explores the emerging role of mitochondria as signaling organelles that communicate with other cellular components, particularly the nucleus, under various stress conditions. Traditional views of mitochondria as mere energy producers are being redefined, highlighting their multifaceted functions in cellular homeostasis and stress response. The authors discuss the mechanisms by which mitochondria generate and transmit signals to the nucleus, such as acetyl-CoA, reactive oxygen species (ROS), calcium ions, and the mitochondrial unfolded protein response (UPRmt). These signals play crucial roles in regulating gene expression, promoting adaptive stress responses, and influencing longevity and disease susceptibility. The article also delves into the discovery of mitochondria-derived peptides (MDPs) encoded within the mitochondrial genome, which have been implicated in various biological processes and potential therapeutic applications. The review concludes by emphasizing the importance of understanding mitonuclear communication in the context of aging, disease, and therapeutic interventions.This review article explores the emerging role of mitochondria as signaling organelles that communicate with other cellular components, particularly the nucleus, under various stress conditions. Traditional views of mitochondria as mere energy producers are being redefined, highlighting their multifaceted functions in cellular homeostasis and stress response. The authors discuss the mechanisms by which mitochondria generate and transmit signals to the nucleus, such as acetyl-CoA, reactive oxygen species (ROS), calcium ions, and the mitochondrial unfolded protein response (UPRmt). These signals play crucial roles in regulating gene expression, promoting adaptive stress responses, and influencing longevity and disease susceptibility. The article also delves into the discovery of mitochondria-derived peptides (MDPs) encoded within the mitochondrial genome, which have been implicated in various biological processes and potential therapeutic applications. The review concludes by emphasizing the importance of understanding mitonuclear communication in the context of aging, disease, and therapeutic interventions.