Tissue mitochondrial activity dictates the macrophage pool size
Removal of cellular waste from the extracellular space is fundamental for tissue health. Because the rate of material ejected by parenchymal cells varies across tissues, we searched for mechanisms that couple waste production and removal. Here, we show that the uptake of parenchyma-released mitochondria by macrophages is prominent across organs that rely on oxidative respiration-including heart, skeletal muscle, and brown adipose tissue-and that macrophage numbers closely align with the mitochondrial activity of each of these organs. We found that the mitochondrial activity of myofibers dictates the abundance of macrophages by modulating colony-stimulating factor 1 (CSF1) availability and the number of CSF1-producing fibroblasts in the tissue. Consequently, inhibition of CSF1-CSF1 receptor (CSF1R) signaling depleted macrophages and collapsed the mitochondrial activity of skeletal muscles. We propose that, by coupling macrophage abundance to the mitochondrial activity of their parenchyma, tissues ensure efficient waste disposal and fitness.
Authors
- Jorge Alegre‐Cebollada (ORCID: https://orcid.org/0000-0003-0542-0170)
- José Antonio Enrı́quez (ORCID: https://orcid.org/0000-0002-3671-2961)
- Jon Sicilia (ORCID: https://orcid.org/0000-0002-5073-9132)
- Pura Muñoz‐Cánoves (ORCID: https://orcid.org/0000-0002-7533-9047)
- Juan Antonio López (ORCID: https://orcid.org/0000-0002-9097-6060)
- Joan Isern (ORCID: https://orcid.org/0000-0002-1401-9779)
- Silvia Campanario (ORCID: https://orcid.org/0000-0002-9942-2179)
- Miguel Torres (ORCID: https://orcid.org/0000-0003-0906-4767)
- Melanie Greter (ORCID: https://orcid.org/0000-0002-7220-5369)
- Sebastian A. Stifter (ORCID: https://orcid.org/0000-0002-7825-222X)
- Leticia Herrera‐Melle (ORCID: https://orcid.org/0000-0002-9630-2219)
- Cintia Folgueira (ORCID: https://orcid.org/0000-0003-3803-9149)
- Georgiana Crainiciuc (ORCID: https://orcid.org/0000-0002-0912-7425)
- Xiaotong Hong (ORCID: https://orcid.org/0000-0003-1301-1350)
- Roberto Silva‐Rojas (ORCID: https://orcid.org/0000-0002-0349-4283)
- Lorena Esteban‐Martínez (ORCID: https://orcid.org/0000-0002-8163-6259)
- Guadalupe Sabio (ORCID: https://orcid.org/0000-0002-2822-0625)
- Sandra Martín-Salamanca (ORCID: https://orcid.org/0009-0002-3624-4149)
- Laura Pena-Couso (ORCID: https://orcid.org/0000-0002-8665-1618)
- Sofía Vieto (ORCID: https://orcid.org/0000-0002-6969-3605)
- José Ángel Nicolás-Avila (ORCID: https://orcid.org/0000-0002-8301-7216)
- Rafael Romero-Becerra (ORCID: https://orcid.org/0000-0003-3935-2647)
- Jessica Segalés (ORCID: https://orcid.org/0000-0003-3565-0014)
- Jesús Vázquez (ORCID: https://orcid.org/0000-0003-1461-5092)
- Raquel Justo‐Méndez (ORCID: https://orcid.org/0000-0002-7648-3550)
- Andrés Hidalgo (ORCID: https://orcid.org/0000-0001-5513-555X)
- Vera Lukesova
- María Sánchez-Díaz (ORCID: https://orcid.org/0000-0002-8841-3496)
- Antonio L. Serrano (ORCID: https://orcid.org/0000-0002-1476-578X)
- Iván Ballesteros (ORCID: https://orcid.org/0000-0002-6246-2353)
- Macarena De Andrés-Laguillo
- Enrique Calvo (ORCID: https://orcid.org/0000-0001-9096-5233)
- María Gil (ORCID: https://orcid.org/0009-0006-3778-5798)
- Marta León (ORCID: https://orcid.org/0009-0005-4170-341X)
Institutions
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Fleet Science Center (US)
- Universitat Pompeu Fabra (ES)
- University of California, San Francisco (US)
- University of Zurich (CH)
- Instituto de Salud Carlos III (ES)
- Spanish National Centre for Cardiovascular Research (ES)
- Yale University (US)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Centro Nacional de Epidemiología (ES)
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES)
- Universidad Carlos III de Madrid (ES)
- University of San Francisco (US)
Publication Details
- Journal
- Science Immunology
- Published
- 2026-09-04
- DOI
- https://doi.org/10.1126/sciimmunol.aeb9244
- Primary Topic
- Muscle Physiology and Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00