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Mitochondria are eukaryotic cellular organelles that are known to produce energy through a process called oxidative phosphorylation. Besides their primary function, mitochondria are involved in various cellular processes, including cell growth, differentiation, signaling, metabolism, and senescence. Age-related changes cause a decline in mitochondrial quality and integrity due to increased mitochondrial mutations and oxidative damage. Thus, aging can severely impact mitochondrial functions,...
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The nucleus is a membrane-bound organelle that acts as a control center in a eukaryotic cell. It contains chromosomal DNA, which controls gene expression and precisely regulates the production of proteins within the cell. In contrast, the DNA inside the mitochondria and chloroplast only carries out functions that are specific to those organelles.
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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
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A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
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Isolation and Functional Analysis of Mitochondria from Cultured Cells and Mouse Tissue
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Mitochondria power the nucleus under pressure.

Meng Yao1, Yao Zong2, Junjie Gao1

  • 1Institute of Microsurgery on Extremities, And Department of Orthopedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.

Mechanobiology in Medicine
|September 2, 2025
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Summary

Cells under mechanical stress rapidly reposition mitochondria around the nucleus, forming nuclear-associated mitochondria (NAM). This adaptation fuels nuclear ATP production, preserving DNA repair and chromatin accessibility for cell survival.

Keywords:
Mechanical confinementMitochondrial dynamicsNuclear ATP

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Area of Science:

  • Cellular Biology
  • Biophysics
  • Molecular Biology

Background:

  • Mechanical confinement during cell invasion and trafficking threatens nuclear integrity.
  • Cells possess adaptive mechanisms to survive physical stress.

Purpose of the Study:

  • To comment on the biological significance of mitochondria-nucleus repositioning under mechanical stress.
  • To discuss the role of nuclear ATP in maintaining chromatin state and DNA repair.
  • To explore implications for cellular fitness in development and disease.

Main Methods:

  • Observation of mitochondrial relocation to the nucleus under confinement.
  • Analysis of endoplasmic reticulum and actin filament involvement in mitochondrial clustering.
  • Assessment of ATP levels within the nucleus.

Main Results:

  • Mitochondria rapidly cluster around the nucleus (forming nuclear-associated mitochondria, NAM) upon confinement.
  • Endoplasmic reticulum and actin filaments entrap NAM, creating a localized ATP surge.
  • Nuclear ATP fuels chromatin accessibility and DNA damage repair, ensuring cell proliferation.

Conclusions:

  • Mitochondria-nucleus repositioning is a critical adaptive response to mechanical stress.
  • Localized nuclear ATP is vital for maintaining nuclear function and cell viability under pressure.
  • This mechanism has broad implications for understanding cellular fitness in physiological and pathological contexts.