Namrata SOP 1

The Extracellular Matrix Integrates
Mitochondrial Homeostasis
Namrata Mishra*1, Vijeta Bhattacharya 2
School of Pharmacy, ITM University, Turari, Gwalior, Madhya Pradesh
Corresponding Author mail id-
[email protected]
Abstract
The extracellular matrix (ECM) is a dynamic network of proteins

and polysaccharides that provides structural and biochemical
support to surrounding cells. Recent research has illuminated its
crucial role in integrating mitochondrial homeostasis, linking
cellular energy production with tissue health and disease. This
review explores the mechanisms by which the ECM influences
mitochondrial function, highlighting both the advantages and
potential disadvantages of this relationship. Understanding these
interactions opens new avenues for therapeutic strategies targeting
metabolic and degenerative diseases.
Keywords
Extracellular Matrix, Mitochondrial Homeostasis, Cellular

Metabolism, Tissue Engineering, Cell Signaling, Therapeutic
Strategies
Introduction
The extracellular matrix (ECM) is traditionally recognized for its

structural role in tissues, providing scaffolding that supports cellular
integrity. However, emerging evidence suggests that the ECM plays
a pivotal role in regulating mitochondrial homeostasis, the balance
of mitochondrial biogenesis, dynamics, and function. This review
aims to elucidate the complex interplay between the ECM and
mitochondria, emphasizing its implications for cellular metabolism
and tissue health.
Background
Mitochondria are essential organelles responsible for ATP

production through oxidative phosphorylation. They also play a role
in signaling, cellular differentiation, apoptosis, and the control of the
cell cycle and growth. The ECM, composed of proteins such as
collagen, elastin, fibronectin, and laminins, along with
glycosaminoglycans and proteoglycans, influences cellular behavior
through biochemical and mechanical signals. Recent studies have
uncovered that ECM components and remodeling enzymes affect
mitochondrial function and dynamics, suggesting a bidirectional
communication pathway.
Mechanisms of Interaction
1. Biochemical Signaling: ECM molecules can bind to cell

surface receptors, such as integrins, which activate
intracellular signaling cascades impacting mitochondrial
biogenesis and function. For example, fibronectin binding
to integrins can activate pathways involving focal adhesion
kinase (FAK) and mitogen-activated protein kinases
(MAPKs), which influence mitochondrial dynamics and
bioenergetics.
2. Mechanical Signaling: The stiffness and elasticity of the
ECM can affect cellular mechanotransduction pathways.
Changes in ECM stiffness are sensed by cells and
transmitted to mitochondria, affecting their morphology
and function. This mechanical signaling is mediated by the
cytoskeleton and involves proteins like YAP/TAZ, which
translocate to the nucleus and modulate gene expression
related to mitochondrial function.
3. Metabolic Coupling: ECM components can directly
impact cellular metabolism. For instance, hyaluronan, a
glycosaminoglycan in the ECM, has been shown to
modulate glucose uptake and glycolysis, thereby indirectly
affecting mitochondrial function. The interplay between
ECM composition and cellular metabolism can influence
the overall bioenergetic state of the cell.
Advantages
1. Tissue Health and Regeneration: The integration of ECM

and mitochondrial function is crucial for maintaining tissue
health and promoting regeneration. ECM components can
enhance mitochondrial biogenesis and function, improving
cellular energy production and resilience.
2. Adaptation to Environmental Changes: ECM
remodeling in response to environmental cues helps cells
adapt their mitochondrial function accordingly. This
adaptability is vital for cells in dynamic environments, such
as during wound healing or tissue repair.
3. Therapeutic Potential: Understanding ECM-mitochondria
interactions opens new avenues for therapeutic
interventions. Targeting these pathways could enhance
tissue regeneration, combat metabolic disorders, and
improve outcomes in degenerative diseases.
Disadvantages
1. Pathological Remodeling: Abnormal ECM remodeling

can disrupt mitochondrial homeostasis, contributing to
diseases such as fibrosis, cancer, and metabolic disorders.
Excessive ECM deposition or degradation can impair
mitochondrial function, leading to cellular dysfunction and
disease progression.
2. Complexity of Interactions: The intricate and
multifaceted nature of ECM-mitochondria interactions
poses challenges for therapeutic targeting. The
bidirectional communication and involvement of multiple
signaling pathways require a comprehensive understanding
to develop effective treatments.
3. Variability Among Tissues: The composition and
properties of the ECM vary significantly among different
tissues, complicating the extrapolation of findings and
therapeutic strategies from one tissue type to another.
Tailored approaches are necessary to address tissue-
specific ECM-mitochondria dynamics.
Conclusion
The extracellular matrix is more than a structural scaffold; it is a

dynamic regulator of mitochondrial homeostasis, influencing
cellular metabolism and tissue health. While the integration of ECM
and mitochondrial function offers significant advantages for tissue
regeneration and adaptation, pathological remodeling and the
complexity of these interactions present challenges. Continued
research is essential to unravel the precise mechanisms and develop
targeted therapies for metabolic and degenerative diseases.
References
1. Berridge, M. V., & Neuzil, J. (2016). The role of

mitochondria in cellular homeostasis and disease.
Biochemical Journal, 473(5), 431-446.
2. Bonnans, C., Chou, J., & Werb, Z. (2014). Remodelling the
extracellular matrix in development and disease. Nature
Reviews Molecular Cell Biology, 15(12), 786-801.
3. Frantz, C., Stewart, K. M., & Weaver, V. M. (2010). The
extracellular matrix at a glance. Journal of Cell Science,
123(24), 4195-4200.
4. Hynes, R. O. (2009). The extracellular matrix: Not just
pretty fibrils. Science, 326(5957), 1216-1219.
5. Humphries, J. D., Byron, A., & Humphries, M. J. (2006).
Integrin ligands at a glance. Journal of Cell Science,
119(19), 3901-3903.
6. Lu, P., Takai, K., Weaver, V. M., & Werb, Z. (2011).
Extracellular matrix degradation and remodeling in
development and disease. Cold Spring Harbor Perspectives
in Biology, 3(12), a005058.

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The Extracellular Matrix Integrates

School of Pharmacy, ITM University, Turari, Gwalior, Madhya Pradesh

Corresponding Author mail id-

The extracellular matrix (ECM) is a dynamic network of proteins

Extracellular Matrix, Mitochondrial Homeostasis, Cellular

The extracellular matrix (ECM) is traditionally recognized for its

Mitochondria are essential organelles responsible for ATP

1. Biochemical Signaling: ECM molecules can bind to cell

1. Tissue Health and Regeneration: The integration of ECM

1. Pathological Remodeling: Abnormal ECM remodeling

The extracellular matrix is more than a structural scaffold; it is a

1. Berridge, M. V., & Neuzil, J. (2016). The role of

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