bims-tofagi 2026-07-12 papers

Issue of 2026–07–12
four papers selected by
Michele Frison, University of Cambridge

Sci Adv. 2026 Jul 10. 12(28): eaef6631

ER-mitochondria tether ML1 coordinates peripheral fission and wholesale mitophagy for plant adaptation to carbon starvation.

Benhui Shi, Baolei Li, Songyang Wang, Xu Zhang, Yu Tang, Jun Jiang, Liting Zhai, Yang Shao, Jiaqi Sun.

Plants frequently encounter carbon starvation from extended darkness or canopy shading or in nonphotosynthetic tissues, requiring rapid mitochondrial remodeling to match reduced metabolic flux. Here, we reveal a coordinated program integrating peripheral fission-mediated damage segregation and wholesale mitophagy. Carbon starvation triggers a shift from symmetric midzone fission to asymmetric peripheral fission, generating small depolarized fragments alongside larger polarized mitochondria. Unexpectedly, damage-independent wholesale mitophagy targets medium-sized mitochondria for both burden reduction and resource mobilization while excluding small peripheral fission products. We identify mitochondria-ER (endoplasmic reticulum) linker 1 (ML1), a carbon starvation-inducible ER-mitochondria tether, as the central coordinator. At ER-mitochondria contact sites, ML1 promotes peripheral fission and recruits ATG18a (autophagy-related protein 18a) for wholesale mitophagy. Loss of ML1 impairs this coordinated remodeling, resulting in elongated mitochondria, compromised function, and hypersensitivity to carbon starvation. These findings reveal how plants achieve rapid metabolic adaptation through coordinated mitochondrial remodeling.

DOI: https://doi.org/10.1126/sciadv.aef6631

J Cell Biol. 2026 Sep 07. pii: e202511211. [Epub ahead of print]225(9):

Intercellular mitochondrial transfer and trans-mitophagy in response to protein import dysfunction.

Emily Glover, Beth Wiseman, Celyn Dugdale, Charlie Humphery, Lorena Sueiro Ballesteros, Lorna Hodgson, Kevin Wilkinson, Ian Collinson.

Mitochondrial protein import is critical for organelle biogenesis, maintenance, and regeneration-essential for cellular homeostasis. Import dysfunction compromises cellular energy supplies, which is damaging to cells, particularly those with high energetic demands like neurons. Previously, we have shown that import failure is rescued by intercellular mitochondrial transfer (IMT) via tunnelling nanotubes (TNTs) however, the fate of the transferred mitochondria and the mechanistic basis for rescue were unresolved. Here, we show that bidirectional mitochondrial trafficking between cells harboring import-defective and import-competent mitochondria is distinct in terms of their regulation and ensuing consequences. Transferred import-defective mitochondria are highly fragmented and destined for canonical lysosomal degradation. In contrast, reactive oxygen species (ROS)-producing mitochondria at the periphery of cells with import-competent mitochondria are transferred into neighboring cells undergoing import failure. These new arrivals then accumulate within previously uncharacterized "mitochondrial degradation bodies" (MDBs). We speculate that the cooperation of these distinct cases of TNT-mediated conventional and noncanonical "trans-mitophagy" instigates mitochondrial regeneration, and thereby rescues mitochondrial function.

DOI: https://doi.org/10.1083/jcb.202511211

Autophagy. 2026 Jul 09.

NAD+ modulates REST isoform expression and its downstream mitophagy in Alzheimer's disease.

Maria J Lagartos-Donate, Beatriz Escobar-Doncel, Caroline Shi-Qi Zhang, Evandro Fei Fang.

Repressor Element 1-Silencing Transcription factor (REST) emerges as a metabolism-sensitive transcriptional hub that supports basal mitophagy, mitochondrial quality, and synaptic function in neurons. In Alzheimer's disease, REST becomes mislocalized and functionally impaired, coinciding with early defects in mitochondrial quality control. Activation of the NAD+ -SIRT1 axis enhances REST nuclear activity, restores its mitochondrial and neuroprotective gene programs, and attenuates pathological and cognitive decline in experimental AD models. Our study highlights REST as a promising target to preserve mitochondrial and neuronal function.Abbreviations:Alzheimer's disease, AD; Repressor Element 1-Silencing Transcription factor, REST; Nicotinamide Adenine Dinucleotide, NAD+.

Keywords: Alzheimer’s disease; NAD+; REST; SIRT1; transcriptional regulation

DOI: https://doi.org/10.1080/15548627.2026.2701599

Mol Neurobiol. 2026 Jul 10. pii: 753. [Epub ahead of print]63(1):

SUMOylation in Mitochondrial Quality Control: Mechanisms and Implications for Neurodegenerative Disease.

Qingya Wu, Dengying Fan, Jianhui Ren, Yafang Xing, Zhengzheng Chen, Haochen Jin, Yisheng Lu, Xiaopeng Wang, Hua Zheng.

Mitochondria, as the primary energy-generating organelles in neurons, play a pivotal role in regulating cellular metabolism. Given the post-mitotic nature and long lifespan of neurons, they are particularly vulnerable to the cumulative burden of mitochondrial damage. In response to various physiological and stress signals, a sophisticated mitochondrial quality control (MQC) system has evolved, which encompasses mitochondrial biogenesis, dynamics (fission and fusion), and mitophagy. This coordinated network acts as a critical surveillance mechanism to eliminate damaged components and maintain a healthy mitochondrial pool. The small ubiquitin-like modifier (SUMO) pathway, involving reversible SUMOylation and deSUMOylation, has emerged as a key regulator of MQC by directly modifying its core components. Dysregulation of the SUMO pathway disrupts mitochondrial homeostasis, and the resulting mitochondrial dysfunction is increasingly recognized as a central pathogenic mechanism in neurodegenerative diseases. This review systematically examines the role of the SUMO pathway in regulating MQC and its implications in the pathogenesis of Alzheimer's disease, Parkinson's disease, and Huntington's disease. Finally, we discuss the therapeutic potential and translational challenges of targeting the SUMO pathway for the treatment of neurodegenerative diseases.

Keywords: Mitochondrial biogenesis; Mitochondrial dynamics; Mitophagy; Neurodegenerative diseases; SUMOylation

DOI: https://doi.org/10.1007/s12035-026-06050-0