Systemic Haploinsufficiency Mitigates Cardiac Mitochondrial Dysfunction Induced by Cardiomyocyte-Specific Haploinsufficiency via Potential Inter-Organ Crosstalk.

Efficient mitochondrial matrix protein quality control (mPQC), regulated by the mitochondrial matrix protease LONP1, is essential for preserving cardiac bioenergetics, particularly in post-mitotic cardiomyocytes, which are highly susceptible to mitochondrial dysfunction. While cardiac mPQC defects could impair heart function, it remains unclear whether such defects can be mitigated through inter-organ crosstalk by modulating mPQC in extra-cardiac tissues, a potentially valuable strategy given the challenges of directly targeting the heart. To investigate this, we examined two mouse models of haploinsufficiency at young adulthood: a cardiomyocyte-specific heterozygous knockout () and a whole-body heterozygous knockout ().

Aging triggers mitochondrial, endoplasmic reticulum, and metabolic stress responses in the heart.

Introduction: Aging is a multifaceted biological process characterized by a progressive decline in cellular and tissue function. It significantly impacts the cardiovascular system and contributes to the onset of cardiovascular diseases. The mitochondria (mt) and the endoplasmic reticulum (ER) play synergistic roles in maintaining cellular homeostasis and energy production in the heart.