Regulatory Mechanisms of Mitochondrial Volume in the Heart in Response to Physiological and Pathological Stimuli

Chapa-Dubocq, Xavier R. and Rodríguez-Graciani, Keishla M. and Muniz, Joseph Capella and Bazil, Jason N. and Escobales, Nelson and Javadov, Sabzali (2024) Regulatory Mechanisms of Mitochondrial Volume in the Heart in Response to Physiological and Pathological Stimuli. In: Innovations in Biological Science Vol. 7. B P International, pp. 71-134. ISBN 978-81-976007-5-3

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In addition to the critical role in energy metabolism, mitochondria participate in regulating ion homeostasis, redox state, cell proliferation, differentiation, and lipid synthesis. Central to these functions is the inner mitochondrial membrane (IMM), which is crucial for mitochondrial metabolism and overall function. The IMM is densely packed with proteins, comprising over 70% of its mass, that are essential for the electron transport chain, oxidative phosphorylation, energy transfer, and ion transport. The volume of the mitochondrial matrix is a pivotal factor in the structural and functional adaptation of the IMM, both under normal conditions and in response to pathological stress. Various ion transport mechanisms, particularly those involving potassium (K+) and calcium (Ca2+), regulate the osmotic pressure and volume of the matrix. Minor fluctuations in matrix volume can significantly impact the IMM’s plasticity and stimulate mitochondrial bioenergetics through multiple pathways. However, excessive matrix swelling can disrupt the structural integrity of the IMM by deforming the cristae, potentially leading to cell death mediated by mitochondria. This process is often linked to the opening of mitochondrial permeability transition pores, a phenomenon triggered by elevated matrix Ca2+ levels. Despite extensive research, the exact molecular identity of these pores remains unknown. In contrast to Ca2+, increased matrix K+ levels do not induce pore opening in the absence of elevated Ca2+ and may even provide protective effects. Despite significant research efforts, the detailed molecular mechanisms that govern matrix volume changes and IMM structural remodeling in response to energy demands and oxidative stress remain elusive. This review aims to synthesize and discuss existing studies that elucidate the regulatory mechanisms of mitochondrial matrix volume, the remodeling of the IMM, and the interplay between these processes.

Item Type: Book Section
Subjects: Library Keep > Biological Science
Depositing User: Unnamed user with email
Date Deposited: 05 Jul 2024 10:06
Last Modified: 05 Jul 2024 10:06

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