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Related Concept Videos

Mitochondria01:37

Mitochondria

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,...
Mitochondria01:37

Mitochondria

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,...
Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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.
Most of the mitochondrial precursors...
Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Mitochondrial Membranes01:45

Mitochondrial Membranes

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,...
Mitochondrial Membranes01:45

Mitochondrial Membranes

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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Mitochondrial Respiration Quantification in Yeast Whole Cells
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Mitochondrial Respiration Quantification in Yeast Whole Cells

Published on: November 8, 2024

Isoflavones promote mitochondrial biogenesis.

Kyle A Rasbach1, Rick G Schnellmann

  • 1Medical University of South Carolina, Department of Pharmaceutical and Biomedical Sciences, South Carolina College of Pharmacy, 280 Calhoun St., P.O. Box 250140, Charleston, SC 29425, USA.

The Journal of Pharmacology and Experimental Therapeutics
|February 13, 2008
PubMed
Summary

Several isoflavones promote mitochondrial biogenesis in kidney cells by increasing PGC-1alpha and SIRT1, aiding recovery from injury. These compounds offer potential therapeutic strategies for cell damage, independent of estrogen receptors.

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Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Mitochondrial damage is a key factor in cell injury from toxins, hypoxia, or trauma.
  • Enhanced mitochondrial biogenesis accelerates functional recovery in injured renal proximal tubular cells (RPTCs).
  • Few pharmacological agents are known to effectively increase mitochondrial biogenesis.

Purpose of the Study:

  • To identify pharmacological agents that can increase mitochondrial biogenesis.
  • To investigate the role of isoflavones in promoting mitochondrial biogenesis and cellular recovery.
  • To elucidate the mechanisms underlying isoflavone-induced mitochondrial biogenesis, including the involvement of PGC-1alpha and SIRT1.

Main Methods:

  • Treatment of RPTCs with various isoflavone derivatives and related compounds.
  • Measurement of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1alpha expression.
  • Assessment of mitochondrial biogenesis markers, including ATP synthase beta, ND6 expression, cellular respiration, and ATP production.
  • Evaluation of estrogen receptor involvement using ICI182780 (fulvestrant).
  • Analysis of sirtuin (SIRT)1 expression and activity in response to isoflavone treatment.

Main Results:

  • Daidzein, genistein, biochanin A, formononetin, DCHC, 7-C, 4',7-D, and 5,7,4'-T increased PGC-1alpha expression and induced mitochondrial biogenesis in RPTCs.
  • These compounds led to increased ATP synthase beta and ND6 expression, with a 1.5-fold rise in respiration and ATP levels.
  • Isoflavone-induced mitochondrial biogenesis was independent of estrogen receptor signaling.
  • Isoflavone derivatives exhibited differential effects on SIRT1, with some inducing expression and/or activation, crucial for PGC-1alpha regulation.
  • Specific structural features of isoflavones were identified as critical for SIRT1 activation and expression.

Conclusions:

  • A series of substituted isoflavones effectively promote mitochondrial biogenesis through PGC-1alpha and modulated SIRT1 activity/expression.
  • These isoflavones represent a novel class of compounds that can enhance cellular recovery from injury independently of estrogen receptors.
  • Understanding the structure-activity relationships of isoflavones provides a basis for developing targeted therapies for mitochondrial dysfunction.