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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,...
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Translocation of Proteins into the Mitochondria

Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
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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,...
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Electron Transport Chains

The final stage of cellular respiration is oxidative phosphorylation that consists of two steps: the electron transport chain and chemiosmosis. The electron transport chain is a set of proteins found in the inner mitochondrial membrane in eukaryotic cells. Its primary function is to establish a proton gradient that can be used during chemiosmosis to produce ATP and generate electron carriers, such as NAD+ and FAD, that are used in glycolysis and the citric acid cycle.
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Peroxisomes and mitochondria are two important oxygen-utilizing organelles in eukaryotic cells. Mitochondria carry out cellular respiration—the process that converts energy from food into ATP. Peroxisomes carry out a variety of functions, primarily breaking down different substances, such as fatty acids.The peroxisome is a single membrane-bound cellular organelle that can perform several different functions, including lipid metabolism and chemical detoxification. The enzymes within peroxisomes...
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An Improved Method to Isolate Mitochondrial Contact Sites
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Published on: June 16, 2023

Mitochondria-ER contacts function as an iron supply hub.

Hijiri Oshio1, Isshin Shiiba2,3, Naoki Ito1

  • 1Laboratory of Molecular Biochemistry, Department of Life Science, Faculty of Science, Gakushuin University, Toshima, Tokyo, Japan.

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This study reveals how heme provides iron to mitochondria via mitochondria-endoplasmic reticulum contact sites (MERCs). The enzyme heme oxygenase 2 (HMOX2), regulated by MITOL, ensures mitochondrial iron homeostasis and respiration.

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Area of Science:

  • Cellular Biology
  • Mitochondrial Biology
  • Metabolic Homeostasis

Background:

  • Mitochondrial iron dynamics are crucial for cellular respiration and metabolic balance.
  • The precise mechanisms for iron delivery into mitochondria are not fully understood.
  • Mitochondria-endoplasmic reticulum contact sites (MERCs) are emerging as key regulatory hubs in cellular processes.

Purpose of the Study:

  • To elucidate the molecular mechanisms of iron supply to mitochondria.
  • To identify the role of heme as an iron source for mitochondria.
  • To investigate the regulation of mitochondrial iron homeostasis at MERCs.

Main Methods:

  • Localization studies of heme oxygenase 2 (HMOX2) at MERCs.
  • Analysis of MITOL-mediated ubiquitination of HMOX2.
  • Assessment of mitochondrial iron levels and respiration in knockout/mutant models.
  • Investigation of mitochondrial supercomplex integrity.

Main Results:

  • Heme serves as a direct iron source for mitochondria, regulated at MERCs.
  • HMOX2, an ER-resident enzyme, localizes to MERCs and supplies mitochondrial iron.
  • MITOL ubiquitinates HMOX2, enhancing its heme-degrading activity and iron supply.
  • Disruption of HMOX2 or MITOL impairs mitochondrial iron homeostasis and respiration.

Conclusions:

  • MERCs act as a critical hub for iron supply, integrating heme metabolism with mitochondrial iron utilization.
  • MITOL-mediated regulation of HMOX2 at MERCs is essential for maintaining mitochondrial iron homeostasis.
  • This pathway is vital for cellular respiration and overall metabolic health.