Next, the 1,121 proteins identified via cICAT analysis were evaluated by a systematic data-integrative approach to select more reliable mt proteins ( Figure 1A ). First, we examined the Gene Ontology (GO) cellular component annotation for the identified proteins and compiled 13 reference mt protein datasets from seven mt proteins databases and six mt proteomics datasets (see Materials and Methods for details). In total, 569 out of 1,121 proteins (50.76%) were annotated as mitochondrial proteins and observed from at least one reference mt protein dataset ( Figure 1B) . Then, we assessed the physical and functional links of reference mt proteins based on the assumption that protein pairs that interact or share similar functions tend to cluster within the same subcellular organelle [15] . A total of 201 proteins were physically (82 proteins, 7.31%) or functionally (119 proteins, 10.62%) linked to the 569 reference mt proteins ( Figure 1B ). Physical link represents proteinprotein interaction. Meanwhile, functional link represents a relationship between two proteins if they shared a substrate in a metabolic pathway, co-expressed, co-regulated, or involved in the same protein complex. We listed these 770 mt proteins (569+82+119) in Table S1 as a reliable mt protein dataset. Among the 770 mt proteins, the numbers of down-regulated, up-regulated, and not significantly changed proteins were 288, 122, and 360, respectively ( Figure 1C ). The remaining proteins (351 proteins, 31.31%) were assigned as non-referenced mt proteins that might be either novel mt proteins or proteins with localizations that were affected by mtDNA depletion.