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Related Concept Videos

Mitochondrial Membranes01:45

Mitochondrial Membranes

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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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The Inner Mitochondrial Membrane01:28

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The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria.  In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
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Electron Transport Chain: Complex I and II01:46

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The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
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Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
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Mitochondrial Protein Sorting01:39

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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
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Mitochondria01:37

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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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Understanding the Changes in Mitochondrial Morphology through Dynamic and Three-dimensional Fluorescence Micrographs
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Ionic signalling and mitochondrial dynamics.

Nada Abuarab1, Fangfang Li1, Asipu Sivaprasadarao1,2

  • 1School of Biomedical Sciences, Faculty of Biological Sciences, LS2 9JT, Leeds, U.K.

Molecular & Cellular Oncology
|December 7, 2017
PubMed
Summary
This summary is machine-generated.

Increased reactive oxygen species (ROS) fragment mitochondria in aging. Our study shows ROS-activated TRPM2 channels release lysosomal zinc, causing mitochondrial fragmentation, offering therapeutic insights.

Keywords:
TRPM2calciumcell migrationcell proliferationlysosomal membrane permeabilisationmitochondrial dynamicsoxidative stressreactive oxygen specieszinc

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Area of Science:

  • Cellular Biology
  • Mitochondrial Dynamics
  • Age-Related Diseases

Background:

  • Elevated intracellular reactive oxygen species (ROS) are implicated in age-related diseases.
  • Mitochondrial fragmentation is a hallmark of cellular aging and disease.
  • The precise mechanisms linking ROS to mitochondrial fragmentation require further elucidation.

Purpose of the Study:

  • To investigate the role of TRPM2 channels in ROS-induced mitochondrial fragmentation.
  • To elucidate the downstream signaling pathway involving lysosomal zinc release.
  • To explore potential therapeutic targets for age-related mitochondrial dysfunction.

Main Methods:

  • Utilized cellular models to study reactive oxygen species (ROS) signaling.
  • Investigated the function of TRPM2 channels using specific inhibitors and genetic approaches.
  • Assessed lysosomal zinc release and mitochondrial morphology via advanced microscopy techniques.

Main Results:

  • Demonstrated that ROS directly activate TRPM2 channels.
  • Showcased TRPM2 channel activation leading to lysosomal Zn2+ release.
  • Confirmed that lysosomal zinc triggers mitochondrial fragmentation.

Conclusions:

  • ROS-activated TRPM2 channels represent a critical link to mitochondrial fragmentation.
  • Lysosomal zinc release is a key mediator in this process.
  • Targeting the TRPM2-lysosomal-mitochondrial axis may offer therapeutic strategies for aging.