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Mitochondrial Membranes01:45

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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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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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Mitochondrial precursors are partially unfolded or loosely folded polypeptide chains. Newly synthesized precursors are inhibited from spontaneously folding into their native conformation by the cytosolic chaperones, heat shock proteins 70 (Hsp70), and mitochondrial import stimulation factors (MSFs). Precursors bound to MSFs are guided to the TOM70-TOM37 receptors, while precursors bound to Hsp70  chaperones are targetted to TOM20-TOM22 receptor complexes.
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Increased COX-1 expression in benign prostate epithelial cells is triggered by mitochondrial dysfunction.

Chandler N Hudson1, Kai He1, Laura E Pascal1,2,3

  • 1Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine Pittsburgh, PA, USA.

American Journal of Clinical and Experimental Urology
|September 2, 2022
PubMed
Summary

Cyclooxygenase-1 (COX-1) is elevated in benign prostatic hyperplasia (BPH) epithelial cells and linked to CD8+ T-cells. Mitochondrial dysfunction can induce COX-1, suggesting a role in BPH development.

Keywords:
BPHCOX-1COX-2agingprostate inflammation

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Area of Science:

  • Urology
  • Inflammation Research
  • Molecular Biology

Background:

  • Prostatic inflammation is linked to benign prostatic hyperplasia (BPH) development.
  • Studies on cyclooxygenase-2 (COX-2) inhibitors for BPH symptoms show mixed results.
  • Understanding cyclooxygenase roles in BPH and inflammation is crucial.

Purpose of the Study:

  • To investigate the expression and regulation of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in benign prostatic hyperplasia (BPH).
  • To explore the role of mitochondrial dysfunction in COX expression within prostate epithelial cells.
  • To determine the association of COX-1 with specific immune cell infiltrates in BPH.

Main Methods:

  • Immunohistochemistry was used to analyze COX-1 expression in BPH tissues and compare with donor samples.
  • Human prostate cell lines (BPH-1, RWPE-1) were treated with mitochondrial inhibitors (rotenone, MitoQ).
  • RWPE-1 cells underwent knockdown of NDUFS3 (a complex 1 gene) using small interfering RNA.

Main Results:

  • COX-1 expression was increased in BPH epithelial cells and often co-occurred with COX-2 alterations.
  • Elevated COX-1 correlated with CD8+ cytotoxic T-cells but not other inflammatory cells or patient age/prostate size.
  • Mitochondrial dysfunction and NDUFS3 knockdown induced COX protein levels in cell lines.

Conclusions:

  • COX-1 is elevated in BPH epithelial cells and associated with CD8+ T-cells.
  • Mitochondrial complex I inhibition can induce COX-1 in prostate cells.
  • COX-1 and mitochondrial dysfunction may be significant factors in age-related benign prostatic disease.