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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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全身性エリテマトーデスにおけるミトコンドリア機能不全がナチュラルキラー細胞機能不全を駆動する

Natalia W Fluder1, Morgane Humbel2, Emeline Recazens3

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

JCI insight
|February 2, 2026
PubMed
まとめ

全身性エリテマトーデス（SLE）のナチュラルキラー（NK）細胞はミトコンドリアの欠陥を示し、その機能を損なう。ミトコンドリア品質管理をウロリチンAで強化することでNK細胞の活性が回復し、SLEの新たな治療アプローチが示唆される。

キーワード:
自己免疫疾患自己免疫免疫学ループスNK細胞

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科学分野:

  • 免疫学
  • 細胞生物学
  • ミトコンドリア生物学

背景:

  • 全身性エリテマトーデス（SLE）は、免疫調節不全を伴う自己免疫疾患である。
  • ナチュラルキラー（NK）細胞はSLEにおいて機能的に障害されるが、そのメカニズムは不明である。

研究 の 目的:

  • SLE NK細胞障害におけるミトコンドリア機能不全とミトファジーの役割を調査する。
  • SLEにおけるミトコンドリア品質管理を標的とする治療戦略を探る。

主な方法:

  • SLE NK細胞の構造的、代謝的、プロテオミクス的解析。
  • ミトファジー関連遺伝子の転写およびプロテオミクス的プロファイリング。
  • ミトファジー活性化剤（ウロリチンA）およびヒドロキシクロロキンを用いたin vitro試験。

主要な成果:

  • SLE NK細胞は肥大した機能不全のミトコンドリアと障害されたミトファジーを示す。
  • ミトコンドリア品質管理の欠陥は、NK細胞の細胞傷害性とサイトカイン産生の低下と相関する。
  • ウロリチンAはミトコンドリア機能とNK細胞応答を回復させた。
  • ヒドロキシクロロキンはミトコンドリアリサイクリングを部分的に改善した。

結論:

  • ミトファジー障害とミトコンドリア機能不全は、SLEにおけるNK細胞欠陥の主な要因である。
  • ミトコンドリア品質管理経路を標的とすることは、SLEの新規治療戦略を提供する可能性がある。