<i>mito</i>-QC illuminates mitophagy and mitochondrial architecture in vivo

TLDR

Mitophagy is an essential mitochondrial quality‑control mechanism in mammals, yet its occurrence in specific cell types in vivo remains unclear due to a lack of tractable tools. The authors developed mito‑QC, a transgenic mouse with a pH‑sensitive fluorescent mitochondrial signal, to study mitophagy in vivo. Mito‑QC enables in vivo assessment of mitophagy and mitochondrial architecture via a pH‑sensitive fluorescent signal, compatible with confocal microscopy and histochemical methods for single‑cell resolution across organs. The model revealed highly enriched mitophagy zones in the developing heart and specific adult kidney cells, demonstrating mito‑QC’s broad utility for cell biology research.

Abstract

Autophagic turnover of mitochondria, termed mitophagy, is proposed to be an essential quality-control (QC) mechanism of pathophysiological relevance in mammals. However, if and how mitophagy proceeds within specific cellular subtypes in vivo remains unclear, largely because of a lack of tractable tools and models. To address this, we have developed "mito-QC," a transgenic mouse with a pH-sensitive fluorescent mitochondrial signal. This allows the assessment of mitophagy and mitochondrial architecture in vivo. Using confocal microscopy, we demonstrate that mito-QC is compatible with classical and contemporary techniques in histochemistry and allows unambiguous in vivo detection of mitophagy and mitochondrial morphology at single-cell resolution within multiple organ systems. Strikingly, our model uncovers highly enriched and differential zones of mitophagy in the developing heart and within specific cells of the adult kidney. mito-QC is an experimentally advantageous tool of broad relevance to cell biology researchers within both discovery-based and translational research communities.