ミトコンドリアの形状変化がDNA分配を制御する仕組みを解明(How mitochondria organize our “second genome”)

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2026-04-07 スイス連邦工科大学ローザンヌ校(EPFL)

スイス連邦工科大学ローザンヌ校の研究チームは、ミトコンドリアが「第二のゲノム」と呼ばれるミトコンドリアDNA(mtDNA)をどのように組織化しているかを解明した。ミトコンドリア内部では、mtDNAは単に存在するのではなく、特定のタンパク質と結合して構造体(ヌクレオイド)を形成し、効率的な遺伝子発現や複製が可能となっている。研究は、これらの構造が動的に再編成されることで、細胞のエネルギー需要やストレスに応じた柔軟な制御が行われることを示した。さらに、この仕組みの異常が代謝疾患や老化関連疾患に関与する可能性も指摘される。本成果は細胞内エネルギー制御と遺伝情報管理の理解を深め、関連疾患の新たな治療戦略に貢献すると期待される。

ミトコンドリアの形状変化がDNA分配を制御する仕組みを解明(How mitochondria organize our “second genome”)
Pearling in a mitochondrion. Credit: Suliana Manley © 2026 EPFL

<関連情報>

パール形成がミトコンドリアDNAヌクレオイドの分布を促進する Pearling drives mitochondrial DNA nucleoid distribution

Juan C. Landoni, Matthew D. Lycas, Josefa Macuada, Willi Stepp, […] , and Suliana Manley
Science  Published:2 Apr 2026
DOI:https://doi.org/10.1126/science.adu5646

Editor’s summary

Mitochondria contain their own DNA packaged into structures called nucleoids, which must be evenly spaced along the organelle’s network to ensure function and inheritance. Landoni et al. found that this spacing arises from “pearling,” a physical instability that transforms a mitochondrion from a tubule into regularly spaced, connected beads (see the Perspective by van den Ameele and Prudent). Pearling occurs reversibly in response to calcium influx, carrying nucleoids along, splitting them, and leaving them spaced at regular intervals. The frequency and duration of pearling are defined by the dynamic inner mitochondrial membrane architecture, linking mitochondrial physiology to genome organization. —Stella M. Hurtley

Abstract

The distribution of mitochondrial DNA–containing nucleoids is essential for mitochondrial function and genome inheritance; however, no known mechanisms can explain nucleoid segregation or their regular positioning. In this work, we found that mitochondria frequently undergo a reversible biophysical instability termed “pearling,” transforming from a tubular into a regularly spaced beads morphology. Physiological pearling imposed a characteristic length scale and simultaneously mediated nucleoid disaggregation and established internucleoid distancing with high precision. Pearling onset was triggered by calcium influx, whereas the density of lamellar cristae invaginations modulated pearling prevalence and preserved nucleoid spacing following recovery. The dysregulation of mitochondrial calcium influx or inner membrane cristae integrity caused aberrant nucleoid clustering. Our results identify pearling as a mechanism governing nucleoid distribution and inheritance and offer insights into its regulation.

細胞遺伝子工学
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