Journal of inherited metabolic diseaseOct 12, 2026

Inherited Metabolic Diseases and the Role of Selective Cell Recycling

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Oct 13, 2026

Abstract

Selective autophagy may play a crucial role in degrading specific cellular components, including mitochondria and protein aggregates.

Selective autophagy receptors (SARs) facilitate the targeted degradation of damaged or excess cellular materials by linking them to the autophagic machinery.
Mechanistic differences between bulk and selective autophagy involve distinct signaling pathways, receptor networks, and transcriptional programs for cargo clearance.
Dysregulation of selective autophagy pathways is associated with the development of inherited metabolic diseases (IMDs), which affect metabolism and multiple organ systems.
Major forms of selective autophagy include mitophagy, pexophagy, glycophagy, lipophagy, ER-phagy, and ferritinophagy, each with specific roles in cellular maintenance.
Modulating autophagy receptors and signaling pathways could provide therapeutic strategies to restore cellular balance and alleviate symptoms in IMDs.

Simplified

Selective autophagy is increasingly recognized as a fundamental quality-control mechanism that complements bulk autophagy by enabling the targeted degradation of specific intracellular cargos, including mitochondria, endoplasmic reticulum (ER), lipid droplets, glycogen, peroxisomes, ferritin, ribosomes, and protein aggregates. Cargo selectivity is mediated by selective autophagy receptors (SARs), which link damaged or superfluous substrates to the autophagic machinery through LC3/GABARAP interactions, thereby coordinating cargo sequestration. Recent studies have revealed substantial mechanistic differences between bulk and selective autophagy, highlighting the specialized signaling pathways, receptor networks, and transcriptional programs that regulate selective cargo clearance. Dysregulation of these pathways has emerged as a key contributor to the pathogenesis of inherited metabolic diseases (IMDs), a heterogeneous group of genetic disorders characterized by defective metabolism and multisystem involvement. This review summarizes the molecular mechanisms underlying major forms of selective autophagy, including mitophagy, pexophagy, glycophagy, lipophagy, ER-phagy, and ferritinophagy. It also discusses their relevance across IMD classes, such as mitochondrial disorders, lysosomal storage disorders, and peroxisomal diseases, among many others. Furthermore, selective autophagy is highlighted as a potential therapeutic target, with modulation of autophagy receptors and signaling pathways offering promising strategies to restore cellular homeostasis and improve disease manifestations in IMDs.

Full Text

Full text is available at the source.

View Full Text ↗

Inherited Metabolic Diseases and the Role of Selective Cell Recycling

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the longevity & aging brief