Mitochondrial Transport Proteins in Cardiovascular Diseases: Metabolic Gatekeepers, Pathogenic Mediators and
Yue Pei1,2, Sitong Wan1, Jingyi Qi1
1Department of Nutrition and Health, China Agricultural University, Beijing 100193, China.
Insights
Mitochondrial transport proteins are crucial for heart health. Their dysfunction drives cardiovascular diseases (CVDs), but targeting these transporters offers new therapeutic strategies for heart conditions.
Area of Science:
- Cardiovascular Biology
- Mitochondrial Medicine
- Molecular Cardiology
Background:
- Mitochondria are central to cellular energy, redox balance, and calcium signaling, maintaining cardiovascular homeostasis.
- Cardiovascular diseases (CVDs) are a leading cause of death, with mitochondrial dysfunction as a common pathological factor.
- Impaired mitochondrial transport systems disrupt cellular bioenergetics and increase oxidative stress, driving CVD progression.
Purpose of the Study:
- To review the role of mitochondrial transport proteins in cardiovascular disease (CVD) pathogenesis.
- To explore the structural-functional relationships and dysregulation of key mitochondrial transporters in cardiac pathology.
- To evaluate therapeutic strategies targeting mitochondrial transport systems for CVD treatment.
Main Methods:
- Literature review synthesizing current knowledge on mitochondrial transport proteins and their role in CVD.
- Analysis of structural-functional relationships of transporters like VDAC, TRP channels, MCU, and ANT.
- Evaluation of preclinical therapeutic approaches including pharmacological modulation, gene editing, and nanotechnology.
Main Results:
- Mitochondrial transport protein dysfunction contributes to metabolic inflexibility, mitochondrial permeability transition pore destabilization, and programmed cell death in the heart.
- Aberrant transporter activity exacerbates oxidative stress and impairs energy metabolism, key features of cardiac pathology.
- Targeting these transport systems shows promise in preclinical models for treating CVD.
Conclusions:
- Mitochondrial transport systems are critical regulators of cardiac metabolism and function, and their dysfunction is a key driver of CVD.
- Targeting mitochondrial transport proteins offers a promising avenue for developing novel diagnostic biomarkers and precision therapies for cardiovascular diseases.
- Understanding the interplay between transport protein dysfunction and cardiac metabolic reprogramming is essential for advancing CVD treatment strategies.
Abstract:
Mitochondria, as the metabolic hubs of cells, play a pivotal role in maintaining cardiovascular homeostasis through dynamic regulation of energy metabolism, redox balance, and calcium signaling. Cardiovascular diseases (CVDs), including heart failure, ischemic heart disease, cardiomyopathies, and myocardial infarction, remain the leading cause of global mortality, with mitochondrial dysfunction emerging as a unifying pathological mechanism across these conditions. Emerging evidence suggests that impaired mitochondrial transport systems-critical gatekeepers of metabolite flux, ion exchange, and organelle communication-drive disease progression by disrupting bioenergetic efficiency and exacerbating oxidative stress. This review synthesizes current knowledge on mitochondrial transport proteins, such as the voltage-dependent anion channels, transient receptor potential channels, mitochondrial calcium uniporter, and adenine nucleotide translocator, focusing on their structural-functional relationships and dysregulation in CVD pathogenesis. We highlight how aberrant activity of these transporters contributes to hallmark features of cardiac pathology, including metabolic inflexibility, mitochondrial permeability transition pore destabilization, and programmed cell death. Furthermore, we critically evaluate preclinical advances in targeting mitochondrial transport systems through pharmacological modulation, gene editing, and nanoparticle-based delivery strategies. By elucidating the mechanistic interplay between transport protein dysfunction and cardiac metabolic reprogramming, we address a critical knowledge gap in cardiovascular biology and provide a roadmap for developing precision therapies. Our insights underscore the translational potential of mitochondrial transport machinery as both diagnostic biomarkers and therapeutic targets, offering new avenues to combat the growing burden of CVDs in aging populations.
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