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Related Concept Videos

Mitochondria01:37

Mitochondria

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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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Translocation of Proteins into the Mitochondria01:19

Translocation of Proteins into the Mitochondria

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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 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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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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Mitochondrial Precursor Proteins01:39

Mitochondrial Precursor Proteins

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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.
Most of the mitochondrial...
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TFAM promotes mitochondrial division by increasing mitochondrial Sirt3.

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Mitochondrial transcription factor A (TFAM) promotes mitochondrial fission by interacting with Sirtuin 3 (Sirt3), activating the AMPK/MFF/Drp1 pathway. This TFAM-Sirt3 interaction is crucial for regulating mitochondrial morphology and impacts cancer survival.

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A Faster, High Resolution, mtPA-GFP-based Mitochondrial Fusion Assay Acquiring Kinetic Data of Multiple Cells in Parallel Using Confocal Microscopy

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Area of Science:

  • Cell Biology
  • Mitochondrial Dynamics
  • Cancer Research

Background:

  • Mitochondrial transcription factor A (TFAM) is known for its role in mtDNA maintenance.
  • Its function in regulating mitochondrial fission is not fully understood.
  • TFAM's impact on mitochondrial morphology and its underlying mechanisms require further investigation.

Purpose of the Study:

  • To elucidate the mechanism by which TFAM regulates mitochondrial fission.
  • To investigate the interaction between TFAM and Sirtuin 3 (Sirt3) in controlling mitochondrial dynamics.
  • To explore the clinical relevance of TFAM-SIRT3 co-expression in cancer.

Main Methods:

  • Fluorescence and transmission electron microscopy (TEM) in zebrafish embryos and cell lines.
  • Analysis of protein interactions using FRET imaging and co-immunoprecipitation.
  • Western blotting, immunofluorescence, and cellular assays to assess protein localization and activity.
  • TCGA data analysis for cancer patient survival.

Main Results:

  • TFAM modulates mitochondrial fission; knockdown inhibits, while overexpression promotes fragmentation.
  • TFAM directly interacts with Sirt3 via its HMG-box A domain, enhancing Sirt3's mitochondrial localization and deacetylation activity.
  • TFAM-Sirt3 interaction activates the AMPK/MFF/Drp1 pathway, promoting Drp1-dependent mitochondrial fission.
  • High TFAM-SIRT3 co-expression correlates with improved survival in various cancers, notably KIRC.

Conclusions:

  • TFAM is a key regulator of mitochondrial fission through its interaction with Sirt3.
  • This interaction modulates mitochondrial protein deacetylation and activates the AMPK/MFF/Drp1 pathway.
  • The TFAM-Sirt3 axis represents a potential therapeutic target and prognostic biomarker in cancer.