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Open research questions in Autophagy in Disease and Therapy

138 unresolved questions extracted from the limitations and future-work sections of 407 Autophagy in Disease and Therapy papers in our library. Each links back to the study that raised it.

What the literature leaves open

  • The role of mitophagy in sunitinib-resistant renal cancer remains poorly defined. There is a need to understand the transcriptional regulation of receptor-mediated mitophagy in sunitinib-resistant renal cancer cells.

    Transcriptional Regulation of Receptor-Mediated Mitophagy in Sunitinib-Resistant Renal Cancer Cells: Response to Succinic Acid · 2026 · DOI

  • The underlying molecular mechanisms of MnO2 nanoparticles' neuroprotective effects remain insufficiently defined. The role of autophagy in MnO2 nanoparticles' neuroprotective effects is not fully understood.

    Manganese Dioxide Nanoparticles Protect PC12 Cells Against H2O2-Induced Oxidative Stress Injury by Regulating PI3K/Akt-Mediated Autophagy · 2026 · DOI

  • The molecular mechanisms of canagliflozin in mitigating diabetic cardiomyopathy are unclear. The effects of canagliflozin on mitochondrial function in diabetic cardiomyopathy are not well understood. There is a need for more effective treatments for diabetic cardiomyopathy.

    Canagliflozin Mitigates Diabetic Cardiomyopathy through Enhanced PINK1-Parkin Mitophagy · 2024 · DOI

  • The study identifies the challenge of understanding the complex interplay between proteostasis mechanisms. Technical challenges include the need for pre-clinical models that accurately mimic in vivo tumor biology. The paper highlights the challenge of leveraging the crosstalk between Hsp70 and autophagy for therapeutic purposes.

    Hsp70 Negatively Regulates Autophagy via Governing AMPK Activation, and Dual Hsp70-Autophagy Inhibition Induces Synergetic Cell Death in NSCLC Cells · 2024 · DOI

  • However, very few studies have investigated such events in human neurons, due to a lack of models showing aging features.

    Decline in mitochondrial health and lysosomal acidification in human neurons during normal aging · 2026 · DOI

  • In neurons, the effect of aging on intrinsic molecular processes, and how they tie to age-related neurodegeneration remains unclear.

    Decline in mitochondrial health and lysosomal acidification in human neurons during normal aging · 2026 · DOI

  • The clearance of unwanted protein aggregates is essential for maintaining proteostasis and cellular function, particularly in long-lived cells such as neurons, yet the signaling pathways that activate selective autophagy of protein aggregates remain incompletely understood.

    CDKL5 deficiency impairs TBK1-mediated autophagy and clearance of neuronal protein aggregates · 2026 · DOI

  • Triple-negative breast cancer (TNBC) cells face metabolic, proteotoxic and treatment-associated stress, but the mechanisms that determine how stressed cells dispose of intracellular cargo remain incompletely defined.

    Lysosomal-stress-driven cargo-fate switching between autophagic degradation and small extracellular vesicle release in triple-negative breast cancer: a hypothesis and theory article · 2026 · DOI

  • In contrast, definitive switching between terminal death pathways within the same cell population remains insufficiently established.

    Metabolism-Gated Cell Death Switching in Myocardial Ischemia-Reperfusion Injury: From Regulated Death Networks to Precision Cardioprotection · 2026 · DOI

  • However, detailed studies on the underlying mechanisms have not yet been reported.

    Y‐27632 Suppresses the Growth and Migration of Oral Squamous Cell Carcinoma, but Upregulates Autophagy by Suppressing mTOR Effectors · 2025 · DOI

  • BACKGROUND: Autophagy and tumor necrosis factor-alpha (TNF-α) are pivotal in the progression of oral squamous cell carcinoma (OSCC), yet their interplay remains inadequately understood.

    The Reciprocal Regulation Between TNF ‐α and Autophagy for Oral Squamous Cell Carcinoma Progression · 2025 · DOI

  • However, the specific molecular target responsible for autophagy-mediated ICD has not yet been elucidated.

    Oxoisoaporphine Alkaloid Iridium(III) Derivative: An Immunogenic Cell Death Inducer That Engages the Autophagy-Dependent Regulator Cathepsin D · 2025 · DOI

  • Mitophagy, a critical process for mitochondrial quality control, is severely impaired in exhausted CD8 + T cells, yet the underlying mechanisms remain unclear.

    USP30 inhibition augments mitophagy to prevent T cell exhaustion · 2025 · DOI

  • However, the underlying mechanisms remain complex and warrant further investigation.

    mTOR-mediated nutrient sensing and oxidative stress pathways regulate autophagy: a key mechanism for traditional Chinese medicine to improve diabetic kidney disease · 2025 · DOI

  • However, it remains unclear how cells translate oxidative stress signals into adaptive mitophagy responses.

    Mitochondrial ROS triggers mitophagy through activating the DNA damage response signaling pathway · 2025 · DOI

  • However, the detailed molecular mechanism governing the iron-dependent recognition of NCOA4 by HERC2 remains elusive.

    Mechanistic insights into the iron–sulfur cluster-dependent interaction of the autophagy receptor NCOA4 with the E3 ligase HERC2 · 2025 · DOI

  • However, the precise molecular mechanisms underlying the role of autophagy in mediating cold stress remain to be fully elucidated.

    Autophagy deficiency confers freezing tolerance in Arabidopsis thaliana · 2025 · DOI

  • Metabolic and neurological disorders commonly display dysfunctional branched-chain amino acid (BCAA) metabolism, though it is poorly understood how this leads to neurological damage.

    Dysfunctional BCAA degradation triggers neuronal damage through disrupted AMPK-mitochondrial axis due to enhanced PP2Ac interaction · 2025 · DOI

  • However, the precise role of NLRC5, the largest member of this family, in myocardial infarction (MI) remains poorly understood.

    Targeting NLRC5 in cardiomyocytes protects postinfarction cardiac injury by enhancing autophagy flux through the CAVIN1/CAV1 axis · 2025 · DOI

  • The mechanisms by which CRC cells develop resistance to regorafenib remain incompletely understood.

    Autophagy inhibition improves sensitivity to the multi-kinase inhibitor regorafenib in preclinical mouse colon tumoroids · 2025 · DOI

  • However, its clinical benefit is limited to a subset of patients, is typically short-lived, and is often accompanied by significant toxicity.

    Autophagy inhibition improves sensitivity to the multi-kinase inhibitor regorafenib in preclinical mouse colon tumoroids · 2025 · DOI

  • Beclin 1, another subunit of Class III PI3K complex, as well as LC3B and ATG7 have been suggested to activate MITF, the major transcription factor for melanogenic gene expression; however, the underlying molecular mechanisms remain elusive (Lee et al.

    The emerging roles of autophagy in the homeostasis of lysosome-related organelles · 2025 · DOI

  • These LROs colocalize with LC3 and require ATG7 (a component of ATG8-conjugation system) for secretion, however, little is known whether upstream autophagy proteins like ULK1 complex, ATG9, and Class III PI3K complex are necessary, and whether induction of autophagy can promote the secretion of theses LROs.

    The emerging roles of autophagy in the homeostasis of lysosome-related organelles · 2025 · DOI

  • While non-selective autophagy facilitates its intracellular persistence in endothelial cells, the role of selective autophagy in this process remains unclear.

    Porphyromonas gingivalis hijacks mitophagy and lysosomal function to persist in endothelial cells · 2025 · DOI

  • aureus survives within them and suppresses host immune functions remain incompletely understood.

    Staphylococcus aureus induces mitophagy via the HDAC11/IL10 pathway to sustain intracellular survival · 2025 · DOI

Most-cited papers in Autophagy in Disease and Therapy

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138 open questions have been extracted from the limitations and future-work passages of 407 Autophagy in Disease and Therapy papers in our library. Each one below links back to the study that raised it, so you can read the original claim in context.

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