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C. Xie

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Open access Aug 2026

Djp1 is a multifunctional Hsp40 cochaperone for mitochondrial phospholipid metabolism

Mitochondria are cellular energy hubs best known for ATP production via oxidative phosphorylation; however, they also serve as biosynthetic centers for phospholipids. Mitochondrial phospholipids are critical for various cellular processes, and their loss underlies myriad mitochondrial diseases. The critical enzymes underlying these biosynthetic cascades are encoded in the nucleus, translated in the cytosol, and imported into mitochondria. Understanding of mechanisms and factors that ensure precise targeting of proteins to mitochondria has been long overlooked but remains critical. Recently, the J-protein/Hsp40 cochaperone Djp1 has emerged as a key player in mitochondrial protein targeting by promoting the transfer of precursors from the endoplasmic reticulum (ER) surface to mitochondria in a pathway termed ER-SURF. Molecular details regarding how Djp1 recognizes clients and more broadly supports mitochondrial function remain unknown. Using biochemical approaches, proteomics, and thin layer chromatography, we demonstrate that Djp1 is a regulator of Phosphatidylserine decarboxylase 1 (Psd1), an inner mitochondrial membrane resident responsible for mitochondrial phosphatidylethanolamine (PE) production. This regulation of Psd1 biogenesis is dependent on its mitochondrial targeting signal and is specific to Djp1 compared to other members of the Hsp40 family or ER targeting factors. Intriguingly, the combined loss of Djp1 and Psd1 results in a synthetic sick phenotype that unexpectedly reflects a role(s) for Djp1 in proper mitochondrial phospholipid metabolism independent of Psd1. Taken together, these findings expand our understanding of Djp1-dependent mitochondrial protein regulation and unveil Djp1 as important for mitochondrial phospholipid metabolism by multiple mechanisms.

Rashima Prem, Alex Maya-Romero, C. Xie et al. · 0 citations
Preprint Aug 2026

From Chains to Trees: Parent-Conditioned Drafting for Semi-Autoregressive Speculative Decoding

Speculative decoding accelerates LLM inference only when drafted continuations survive target-model verification. Semi-autoregressive drafters such as DSpark predict an entire token block with one backbone forward and refine it with a lightweight Markov head. However, DSpark decodes this block as a single chain, so an early mismatch invalidates the remaining suffix and limits the benefit of large draft blocks. We show that the conditional structure already learned by DSpark can support multiple parent-consistent continuations without retraining or additional backbone passes. We introduce Parent-Conditioned Drafting Tree (PCTree), which uses the pretrained Markov head to score alternative children separately for each concrete parent and allocates a fixed verification budget to the most probable paths. This converts DSpark's linear draft into a tree while preserving its one-pass parallel backbone. Across Qwen3-{4B,8B,14B} and nine benchmarks, at $B{=}7$, measured speedup gains over autoregressive (AR) decoding, relative to matched DSpark, range from $3.1\%$ to $29.5\%$. On Qwen3-4B GSM8K at $B{=}16$, PCTree increases mean acceptance length from $9.41$ to $11.16$ and three-run mean AR speedup from $6.14{\times}$ to $6.60{\times}$. These show that parent-conditioned branching can turn conditional capacity already present in a semi-autoregressive drafter into end-to-end inference gains through an inference-only change.

Zixian Li, Tong Li, C. Xie et al. · 1 citation