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Among all the organelles in an animal cell, only mitochondria have their own independent genomes. Animal mitochondrial DNA is a double-stranded, closed-circular molecule with around 20,000 base pairs. Mitochondrial DNA is unique in that one of its two strands, the heavy, or H, -strand is guanine rich, whereas the complementary strand is cytosine rich and called the light, or L, -strand. Compared to nuclear DNA, mitochondrial DNA has a very low percentage of non-coding regions and is marked by...
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Natural selection is an evolutionary process in which individuals with survival-promoting traits reproduce at higher rates. These favorable traits become more common within a population or species. Naturally selected traits initially arise via random genetic mutations. In order for selection to occur, there must be variation within a population, the trait controlling the variation must be heritable, and there must be an evolutionary advantage for variation in the trait.
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The present-day mitochondrial and chloroplast genomes have retained some of the characteristics of their ancestral prokaryotes and also have acquired new attributes during their evolution within eukaryotic cells. Like prokaryotic genomes, mitochondrial and chloroplast genomes neither bind with histone-like proteins nor show complex packaging into chromosome-like structures, as observed in eukaryotes. Unlike mitotic cell divisions observed in eukaryotic cells, mitochondria and chloroplasts...
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Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
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Many human characteristics, like height, are shaped by both nature—in other words, by our genes—and by nurture, or our environment. For example, chronic stress during childhood inhibits the production of growth hormones and consequently reduces bone growth and height. Scientists estimate that 70-90% of variation in height is due to genetic differences among individuals, and 10-30% of variation in height is due to differences in the environments that individuals experience,...
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A eukaryotic cell can have up to three different types of genetic systems: nuclear, mitochondrial, and chloroplast. During evolution, organelles have exported many genes to the nucleus; this transfer is still ongoing in some plant species. Approximately 18% of the Arabidopsis thaliana nuclear genome is thought to be derived from the chloroplast’s cyanobacterial ancestor, and around 75% of the yeast genome derived from the mitochondria’s bacterial ancestor. This export has occurred...
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Disfunción mitocondrial impulsa la disfunción de las células asesinas naturales en el lupus eritematoso sistémico

Natalia W Fluder1, Morgane Humbel2, Emeline Recazens3

  • 1Division of Immunology and Allergy, University of Lausanne, Lausanne, Switzerland.

JCI insight
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PubMed
Resumen

Las células asesinas naturales (NK) en el lupus eritematoso sistémico (LES) muestran defectos mitocondriales, lo que perjudica su función. La mejora del control de calidad mitocondrial con Urolitina A restauró la actividad de las células NK, lo que sugiere un nuevo enfoque terapéutico para el LES.

Palabras clave:
Enfermedades autoinmunesAutoinmunidadInmunologíaLupusCélulas NK

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Área de la Ciencia:

  • Inmunología
  • Biología Celular
  • Biología Mitocondrial

Sus antecedentes:

  • El lupus eritematoso sistémico (LES) es una enfermedad autoinmune con desregulación inmune.
  • Las células asesinas naturales (NK) están funcionalmente alteradas en el LES, pero los mecanismos no están claros.

Objetivo del estudio:

  • Investigar el papel de la disfunción mitocondrial y la mitofagia en el deterioro de las células NK del LES.
  • Explorar estrategias terapéuticas dirigidas al control de calidad mitocondrial en el LES.

Principales métodos:

  • Análisis estructurales, metabólicos y proteómicos de las células NK del LES.
  • Perfilado transcripcional y proteómico de genes relacionados con la mitofagia.
  • Pruebas in vitro de activadores de la mitofagia (Urolitina A) e hidroxicloroquina.

Principales resultados:

  • Las células NK del LES exhiben mitocondrias agrandadas y disfuncionales y una mitofagia alterada.
  • El control de calidad mitocondrial defectuoso se correlaciona con una reducción de la citotoxicidad y la producción de citoquinas de las células NK.
  • La Urolitina A restauró la función mitocondrial y las respuestas de las células NK.
  • La hidroxicloroquina mejoró parcialmente el reciclaje mitocondrial.

Conclusiones:

  • La mitofagia alterada y la disfunción mitocondrial son contribuyentes clave a los defectos de las células NK en el LES.
  • La orientación de las vías de control de calidad mitocondrial puede ofrecer una nueva estrategia terapéutica para el LES.