Biochemical controls: mitochondrial metabolism control (Introduction)

by David Turell , Monday, October 09, 2023, 18:04 (201 days ago) @ David Turell

MOF enzyme role analyzed:

https://phys.org/news/2023-10-epigenetic-mof-mitochondrial-metabolism.html

"The intricate control of cellular metabolism relies on the coordinated and harmonious interplay between the nucleus and mitochondria. On the one hand, mitochondria are the hub for the production of essential metabolites, which aside from being required to meet the energy demands of the cell, also serve as the building blocks for constructing both genetic and epigenetic landscapes in the nucleus. On the other hand, the majority of mitochondrial metabolic enzymes are encoded by the nuclear genome, making the function of these two organelles highly interdependent on one another.

"Inter-organellar communication is aided by molecules that shuttle between these two compartments. The histone acetyltransferase MOF, an enzyme and a classical epigenetic regulator, is such a wanderer between these two worlds.

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"The study, published in the journal Nature Metabolism, uncovers the critical role of MOF in maintaining mitochondrial integrity through a process called protein acetylation. The findings shed light on the specific machinery responsible for regulating protein acetylation of mitochondrial proteins and deepens the understanding of how cells fine-tune their metabolic output.

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"'In our studies in mice, we identified a unique set of mitochondrial proteins that undergo a change in acetylation status upon loss of MOF and its associated complex members, leading to a cascade of mitochondrial defects, including fragmentation and reduced cristae density, and impaired oxidative phosphorylation," says Guhathakurta.

"Mitochondrial function is essential for cellular energy production and many physiological processes. Dysregulation of mitochondrial physiology and function has been implicated in several diseases such as cancer, heart failure and neurodegenerative disorders.

"Very little is known about how acetylation of mitochondrial proteins alters their biochemical properties and functional consequences. The Freiburg team shows that COX17 is an important target of MOF-mediated acetylation. COX17 helps put together a crucial part of the energy-production process in mitochondria, called complex IV. This complex is vital for producing energy through oxidative phosphorylation in cells.

"We show that acetylation of COX17 stimulates its function, highlighting the importance of protein acetylation in regulating oxidative phosphorylation, whereas loss of its acetylation impairs it, demonstrating an unprecedented gain of function via acetylation of a mitochondrial protein. This represents a significant leap forward in our understanding of how epigenetic regulators such as MOF affect cellular metabolism," says Asifa Akhtar.

"The implications of this discovery are far-reaching, suggesting that the balance of protein acetylation in mitochondria may be a critical factor in protecting cells from metabolic catastrophe.

"This novel insight challenges conventional thinking about the role of epigenetic factors and their impact on cellular function. However, the research not only deepens our understanding of mitochondrial biology. It also sheds light on molecular pathways driving pathologies in a developmental disorder, which may help pave the way for potential therapeutic interventions in the future."

Comment: as research in intracellular functions proceeds, it becomes more and more difficult to assume chance mutations can produce these intricate mechanisms.