Molecular Biology

Engineering ATP Import in Yeast Uncovers a Synthetic Route to Extend Cellular Lifespan

1. Naci Oz
2. Hetian Su
3. Vedat Sari
4. Praveen Patnaik
5. Rohil Hameed
6. Jong Hee Song
7. Derek C Prosser
8. Vyacheslav M Labunskyy
9. Vadim N Gladyshev
10. Nan Hao
11. Alaattin Kaya

• Curated by eLife

  eLife Assessment

  This manuscript addresses an important and conceptually ambitious question by using a synthetic biology strategy to perturb ATP homeostasis in yeast and examine its causal relationship with lifespan. While the experimental approach and lifespan data are intriguing, the current evidence is incomplete and internally inconsistent, particularly regarding intracellular ATP measurements, transporter directionality, mitochondrial dependence, and the proposed mechanistic model. Substantial clarification, additional controls, and further experimentation will be necessary before the main conclusions can be considered robust and the biological significance of the findings can be fully assessed.

Reviewed by eLife

Structural basis for the folding of PINK1 by the HSP90–CDC37 chaperone complex

1. Kei Okatsu
2. Hayato Yamamoto
3. Akinori Okamoto
4. Shinya H Goto
5. Yumiko Nishimoto
6. Yukihiko Sugita
7. Takeshi Noda
8. Shuya Fukai

• Curated by eLife

  eLife Assessment

  This study presents a high-quality cryo-EM structure of the human kinase PINK1 in complex with the HSP90-CDC37 chaperone complex, capturing a partially folded intermediate in which the C-lobe and C-terminal extension are structured while the N-lobe remains unfolded and engaged by the HSP90 clamp. The structural data are broadly consistent with a recently published structure of the same complex, providing useful insight into early steps of PINK1 maturation and highlighting residues linked to familial Parkinson's disease. However, the mechanistic conclusions remain incomplete because the manuscript does not experimentally validate key hypotheses raised by the structure, including the functional roles of the C-lobe interface, the HPNI motif, the C-terminal extension, or the proposed competition between HSP90 and TOM20.

Reviewed by eLife

FRG1 Regulates Nonsense-Mediated mRNA Decay by Modulating UPF1 Levels

1. Ananya Palo
2. Talina Mohapatra
3. Anamika Singh
4. Shithij Thalakkat
5. Suryasikha Mohanty
6. Rajeeb Kumar Swain
7. Manjusha Dixit

• Curated by eLife

  eLife Assessment

  This useful study by Palo et al proposes that FRG1 functions as a negative regulator of Nonsense-Mediated mRNA decay (NMD) by associating with the exon junction complex (EJC) and destabilizing UPF1 independently of DUX4. The authors present solid evidence to dissect the relationship between FRG1 and DUX4 in NMD. However, the evidence to support the claim that FRG1 is a component of the EJC or the NMD machinery is incomplete.

Reviewed by eLife

Specialization of ubiquitin ligases to distinct nucleic acid sensors

1. Ibrahim Syed
2. Sheng Chen
3. David J. Peeler
4. Paul F. McKay
5. Marco A. Briones-Orta
6. Jennifer A. Bohn
7. Robin J. Shattock
8. Daniel Gonçalves-Carneiro

Reviewed by Review Commons