Mitochondrial ion transport mechanisms are pivotal in the regulation of mitochondrial bioenergetics, primarily through the modulation of matrix Ca2+ levels. These changes in Ca2+ concentration directly influence mitochondrial respiration and ATP production under normal physiological conditions [6]. The transport of ions across the mitochondrial membrane not only supports energy production but also plays a crucial role in the response of mitochondria to metabolic demands and stressors. In addition to ion transport, remodeling of the IMM is another critical factor that ensures the maintenance of mitochondrial function and overall cellular homeostasis. These remodeling processes are essential for the mitochondria to adapt to changes in metabolic conditions and to respond effectively to cellular stressors. During ischemia-reperfusion (IR) events, the disruption of the delicate balance between matrix volume changes and IMM remodeling occurs, primarily due to oxidative and energy stress. This disruption leads to significant mitochondrial and cardiac dysfunction. The mechanisms behind these changes involve complex interplays between mitochondrial swelling, ion dysregulation, and structural alterations of the IMM, which can ultimately result in cell death if not properly managed.
Author(s) Details:
Xavier R. Chapa-Dubocq
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
Keishla M. Rodríguez-Graciani
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
Joseph Capella Muniz
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
Jason N. Bazil
Department of Physiology, Michigan State University, East Lansing, MI 48824-1046, USA.
Nelson Escobales
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
Sabzali Javadov
Department of Physiology, School of Medicine, University of Puerto Rico, San Juan, PR, USA.
Recent Global Research Developments in Mitochondrial Role in Cardiac Ischemia-Reperfusion Injury
Mitochondrial Quality Control in Cardiac I/R Injury: New Insights
- Mechanism: Long-term studies confirm that mitochondrial damage is a critical factor in cardiac I/R injury. Mitochondria play a central role in ATP generation, metabolite synthesis, calcium homeostasis, oxidative stress, and cell death.
- Quality Control System: Mitochondria maintain their health through a quality control system that involves modifying processes like fusion, fission, mitophagy, biogenesis, and protein homeostasis.
- Interconnected Machinery: This system is interconnected and associated with pathological changes such as oxidative stress, calcium overload, and endoplasmic reticulum (ER) stress.
- Regulatory Mechanisms: Researchers are exploring the regulatory mechanisms and molecular pathways involved in mitochondrial quality control during cardiac I/R damage [1].
Mitochondrial Dynamics and Cardiac I/R Injury
- Disruptions in Dynamics: Mitochondrial dynamics (fusion, fission, and mitophagy) impact cardiomyocyte survival and mitochondrial function.
- Clinical Implications: Dysregulation of mitochondrial dynamics contributes to cardiac I/R injury, cardiomyopathy, and heart failure [2].
Organ-Specific Variations in Mitochondrial Responses
- Context Matters: Mitochondrial responses to I/R injury vary across different organ systems due to unique mitochondrial structures, bioenergetics, and antioxidative capacities [3] .
Mitochondria in Cardiac Microvascular I/R Injury
- Endothelial Cells: Pathological alterations during cardiac microvascular I/R injury involve mitochondria, including increased mitochondrial reactive oxygen species (mROS) levels and disturbed dynamics [4].
References
- Bai, Y., Wu, J., Yang, Z. et al. Mitochondrial quality control in cardiac ischemia/reperfusion injury: new insights into mechanisms and implications. Cell Biol Toxicol 39, 33–51 (2023). https://doi.org/10.1007/s10565-022-09716-2
- Uchikado Y, Ikeda Y and Ohishi M (2022) Current Understanding of the Pivotal Role of Mitochondrial Dynamics in Cardiovascular Diseases and Senescence. Front. Cardiovasc. Med. 9:905072. doi: 10.3389/fcvm.2022.905072
- Nakamura E, Aoki T, Endo Y, Kazmi J, Hagiwara J, Kuschner CE, Yin T, Kim J, Becker LB, Hayashida K. Organ-Specific Mitochondrial Alterations Following Ischemia–Reperfusion Injury in Post-Cardiac Arrest Syndrome: A Comprehensive Review. Life. 2024; 14(4):477. https://doi.org/10.3390/life14040477
- Wang, J., Toan, S. & Zhou, H. New insights into the role of mitochondria in cardiac microvascular ischemia/reperfusion injury. Angiogenesis 23, 299–314 (2020). https://doi.org/10.1007/s10456-020-09720-2
